Safety and effectiveness of direct-acting antiviral drugs in the treatment of hepatitis C in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) management in Inflammatory Bowel Disease (IBD) is uncertain. The ECCO guidelines 2021 recommended HCV treatment but warn about the risk of IBD reactivation. We aimed to evaluate 1) the effectiveness and safety of direct-acting antivirals (DAAs) in IBD; 2) the interaction of DAAs with IBD drugs. METHODS: Multicentre study of IBD patients and HCV treated with DAAs. Variables related to liver diseases and IBD, as well as adverse events (AEs) and drug interactions, were recorded. McNemar's test was used to assess differences in the proportion of active IBD during the study period. RESULTS: We included 79 patients with IBD and HCV treated with DAAs from 25,998 IBD patients of the ENEIDA registry. Thirty-one (39.2 %) received immunomodulators/biologics. There were no significant differences in the percentage of active IBD at the beginning (n = 11, 13.9 %) or at the 12-week follow-up after DAAs (n = 15, 19 %) (p = 0.424). Sustained viral response occurred in 96.2 % (n = 76). A total of 8 (10.1 %) AEs occurred and these were unrelated to activity, type of IBD, liver fibrosis, immunosuppressants/biologics, and DAAs. CONCLUSIONS: We demonstrate a high efficacy and safety of DAAs in patients with IBD and HCV irrespective of activity and treatment of IBD.

Comparison of visual and passive acoustic estimates of beaked whale density off El Hierro, Canary Islands.

Passive acoustic monitoring (PAM) offers considerable potential for density estimation of cryptic cetaceans, such as beaked whales. However, comparative studies on the accuracy of PAM density estimates from these species are lacking. Concurrent, low-cost drifting PAM, with SoundTraps suspended at 200 m depth, and land-based sightings, were conducted off the Canary Islands. Beaked whale density was estimated using a cue-count method, with click production rate and the probability of click detection derived from digital acoustic recording tags (DTags), and distance sampling techniques, adapted to fixed-point visual surveys. Of 32 870 detections obtained throughout 206 h of PAM recordings, 68% were classified as "certain" beaked whale clicks. Acoustic detection probability was 0.15 [coefficient variation (CV) 0.24] and click production rate was 0.46 clicks s - 1 (CV 0.05). PAM density estimates were in the range of 21.5 or 48.6 whales per 1000 km2 [CV 0.50 or 0.44, 95% confidence interval (CI) 20.7-22.4 or 47-50.9), depending on whether "uncertain" clicks were considered. Density estimates from concurrent sightings resulted in 33.7 whales per 1000 km2 (CV 0.77, 95% CI 8.9-50.5). Cue-count PAM methods under application provide reliable estimates of beaked whale density, over relatively long time periods and in realistic scenarios, as these match the concurrent density estimates obtained from visual observations.

Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib.

Alectinib is a preferred first-line therapy for patients with advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) in several national clinical practice guidelines. The randomized, global, phase III ALEX study has demonstrated significant improvement in progression-free survival for alectinib over crizotinib in treatment-naive ALK-positive NSCLC. It was also the first study to show clinically meaningful improvement in overall survival for a next-generation ALK tyrosine kinase inhibitor relative to crizotinib. The J-ALEX and ALESIA phase III studies confirmed the clinical benefit of alectinib relative to crizotinib in the first-line ALK-positive NSCLC treatment setting in Japanese and Asian patients, respectively. Across these pivotal phase III trials, alectinib had a manageable, well-characterized safety profile. Here, we review the safety and tolerability of long-term alectinib treatment in patients with advanced ALK-positive NSCLC and provide guidance for physicians, based on clinical experience, on the management of the most frequently reported adverse events (AEs). Most AEs associated with alectinib can be managed by dose reduction. Some alectinib-related AEs are not yet fully characterized, including myalgia and peripheral oedema and deciphering their underlying mechanism of action could enhance their management. With longer-term follow-up, the safety profile of alectinib continues to remain consistent in the ALEX study, with no new safety signals observed. Safety and tolerability data from the first-line phase III alectinib trials are also consistent with those observed in clinical trials of alectinib in later-line settings. These results add to the weight of evidence recommending alectinib as a preferred therapy for treatment-naive advanced ALK-positive NSCLC.

Human papillomavirus infection and lung adenocarcinoma: special benefit is observed in patients treated with immune checkpoint inhibitors.

BACKGROUND: Human papilloma virus (HPV) has been associated with the development and modulation of response in a series of neoplasms. In the case of lung adenocarcinoma, its role in etiology and pathogenesis is still controversial. Considering that this infection brings foreign epitopes, it could be of prognostic significance in patients with lung adenocarcinoma treated with immunotherapy. METHODS: In a retrospective cohort study we evaluated the presence of HPV genomic material in lung adenocarcinoma primary lesions with the INNO-LiPA platform. Viral replication was also evaluated by detecting the presence of oncoprotein E6/E7 messenger RNA (mRNA) by quantitative RT-PCR. To confirm possible hypotheses regarding viral oncogenesis, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1 (HIF1) were evaluated with stromal fibrosis and immunoscore. RESULTS: A total of 133 patients were included in the analysis, of whom 34 tested positive for HPV, reaching an estimated prevalence of 25.6% [95% confidence interval (CI) 18.2% to 32.9%]. E6/7 mRNA was identified in 28 out of the 34 previously positive cases (82.3%). In immune checkpoint inhibitor (ICI)-treated patients, the median overall survival reached 22.3 months [95% CI 19.4 months- not reached (NR)] for HPV-negative and was not reached in HPV-positive (HPV+) ones (95% CI 27.7-NR; P = 0.008). With regard to progression-free survival, HPV- patients reached a median of 9.2 months (95% CI 7.9-11.2 months) compared to 14.3 months (95% CI 13.8-16.4 months) when HPV was positive (P = 0.001). The overall response rate for HPV+ patients yielded 82.4% compared to 47.1% in negative ones. No differences regarding programmed death-ligand 1, VEGF, HIF1, stromal fibrosis, or immunoscore were identified. CONCLUSIONS: In patients with HPV+ lung adenocarcinoma, a significant benefit in overall response and survival outcomes is observed.

Final efficacy and safety data, and exploratory molecular profiling from the phase III ALUR study of alectinib versus chemotherapy in crizotinib-pretreated ALK-positive non-small-cell lung cancer.

BACKGROUND: At the primary data cut-off, the ALUR study demonstrated significantly improved progression-free survival (PFS) and central nervous system (CNS) objective response rate (ORR) with alectinib versus chemotherapy in pretreated, advanced anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer. We report final efficacy and safety data, and exploratory molecular profiling. PATIENTS AND METHODS: Patients who received prior platinum-doublet chemotherapy and crizotinib were randomized 2 : 1 to receive alectinib 600 mg twice daily (n = 79) or chemotherapy (pemetrexed 500 mg/m2 or docetaxel 75 mg/m2, every 3 weeks; n = 40) until progressive disease, death or withdrawal. The primary endpoint was investigator-assessed PFS. Secondary endpoints included ORR, CNS ORR and safety. Plasma samples were collected at baseline, then every 6 weeks until progressive disease; molecular factors detected by next-generation sequencing were correlated with outcomes. RESULTS: Investigator-assessed PFS was significantly longer with alectinib than chemotherapy (median 10.9 versus 1.4 months; hazard ratio 0.20, 95% confidence interval 0.12-0.33; P < 0.001). ORR was 50.6% with alectinib versus 2.5% with chemotherapy (P < 0.001). In patients with measurable CNS metastases at baseline, CNS ORR was 66.7% with alectinib versus 0% with chemotherapy (P < 0.001). No new safety signals were seen. ALK rearrangement was identified in 69.5% (n = 41/59) of baseline plasma samples. Confirmed partial responses were observed with alectinib in 6/11 patients with a secondary ALK mutation and 4/6 patients with a non-EML4-ALK (where EML4 is echinoderm microtubule-associated protein-like 4) fusion. Detection of mutant TP53 in baseline plasma resulted in numerically shorter PFS with alectinib (hazard ratio 1.88, 95% confidence interval 0.9-3.93). CONCLUSIONS: Final efficacy data from ALUR confirmed the superior PFS, ORR and CNS ORR of alectinib versus chemotherapy in pretreated, advanced ALK-positive non-small-cell lung cancer. Alectinib prolonged PFS versus chemotherapy in patients with wild-type or mutant TP53; however, alectinib activity was considerably decreased in patients with mutant TP53.

Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Afecciones cutáneas en trabajadores con empleos de subsistencia y su relación con factores socioambientales y laborales. Medellín, Colombia / Skin conditions in workers with subsistence jobs and related socio-environmental and labor factors. Medellin Colombia

Introducción: La información acerca de lesiones en piel y sus factores asociados, en trabajadores informales en América Latina y el Caribe aun es escasa. Objetivo: Determinar la relación existente entre las condiciones sociodemográficas, ambientales, laborales y la prevalencia de afecciones en la piel auto-reportada por trabajadores informales “venteros” del centro de Medellín. Material y Métodos: Estudio transversal con intención analítica y fuente primaria de información. Se incluyeron 686 trabajadores. Se aplicó encuesta asistida, previa realización de prueba piloto y estandarización de los encuestadores. Variable dependiente; prevalencia de afecciones en piel. Variables independientes; condiciones laborales, sociodemográficas y ambientales. Se realizó control de errores con análisis estadísticos y sesgos de selección e información. Se realizaron análisis univariado, bivariado y multivariado. Resultados: Trabajadores fundamentalmente hombres (57.6%), edades entre 45-59 años, 60,0% procedente de zona rural. Trabajaban > 8 horas/día (80,6%), toda la semana, con > 20 años (50,7%) en su labor. El 72,2% no utilizaba mecanismos de protección personal. 61,5% consideraba que la contaminación ambiental afectaba su labor y su salud. 19,83% presentó afectaciones cutáneas, como; alergias (12,0%), prurito y sarpullido. Menor prevalencia de alergias en hombres (24,0%) y ≥ 60 años. Mayores prevalencias en quienes laboraban >8 horas/día (94,0%), toda la semana (43,0%), con exposición a sustancias químicas (RP=1,88.IC=1,11;3,20), vendedores de mercancía y cacharro (RP =2,06.IC: 1,08;3,91). Conclusión: Explican mayor prevalencia de alergias proceder de la zona urbana, vender mercancía y cacharro, trabajar >8 horas/día, toda la semana, exponerse a sustancias químicas, considerar que la calidad del aire afecta su labor, y presentar comorbilidades (AU)

Introduction: The information on skin lesions and their associated factors in informal workers in Latin America is scarce. Objective: To determine the existing relationship between sociodemographic, environmental and labor conditions and the prevalence of skin conditions, self-reported by informal workers “venteros” from the Medellin downtown. Material and Methods: Cross-sectional study with analytical intention and primary source of information. 686 workers were included. An assisted survey was applied, after conducting a pilot test and standardization of the interviewers. The presence of skin conditions was considered as the dependent variable and the working, sociodemographic and environmental conditions as independent variables. Error control was performed with statistical analysis, selection and information biases were controlled. Univariate and bivariate analysis was performed. Results: Mainly male workers (57.6%), ages 45-59 years, 60.0% from rural areas. They worked> 8 hours / day (80.6%), all week, with> 20 years (50.7%) in their work. 72.2% did not use personal protection mechanisms. 61.5% considered that environmental pollution affected their work and their health. 19.83% presented skin affectations, such as allergies (12.0%), pruritus and rash. Lower prevalence of allergies in men (24.0%) and ≥60 years. Higher prevalences in those who worked> 8 hours / day (94.0%), all week (43.0%), with exposure to chemical substances (PR = 1.88, IC = 1.11, 3.20), sellers of merchandise and equipment (PR = 2.06.IC: 1.08; 3.91). Conclusion: They explain a higher prevalence of allergies coming from the urban area, selling merchandise and junk, working> 8 hours / day, all week, being exposed to chemical substances, considering that air quality affects their work, and presenting comorbidities (AU)

Electronic nicotine delivery systems (ECs) and COVID-19: the perfect storm for young consumers

The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection (AU)

Electronic nicotine delivery systems (ECs) and COVID-19: the perfect storm for young consumers.

The COVID-19 pandemic caused a change in our society and put health systems in crisis worldwide. Different risk factors and comorbidities have been found that increase the risk of mortality when acquiring this infection. The use of alternative devices to the cigarette like the electronic cigarettes, the vapers have been studied widely and generators of great controversy since it has been discovered that they also produce different pulmonary affections. When developing the SARS-CoV2 infection, different theories have been generated about the greater predisposition to a worse prognosis of people who use electronic cigarettes; however, the information on this continues in discovery. A group of experts made up of oncologists, infectologists, pulmonologists, and epidemiologists met to review the literature and then generate theories about the impact of electronic cigarettes on SARS-CoV2 infection.

Thermal properties and volatile compounds profile of commercial dark-chocolates from different genotypes of cocoa beans (Theobroma cacao L.) from Latin America.

There is a growing interest in the identification of chemometric markers that allow the distinction and authentication of dark-chocolates according to their cocoa geographical origin and/or genotype. However, samples derived from Latin American cocoa, including specimens from North and South America, have not been studied in this context. An exploration of the melting behavior, fat composition, bioactive content, and volatile profile of commercial darkchocolates was conducted to identify possible patterns related to the genotype and/or origin of cocoa from Latin America. The melting properties were evaluated by DSC and related to fat content and fatty acids profile. Total polyphenol, anthocyanin, methylxanthine, and catechin content were analyzed. Finally, the volatile compounds were extracted and identified by HS-SPME/GC-MS and were analyzed through Principal Component Analysis (PCA) and the Hierarchical Cluster Analysis Heatmap (HCA Heatmap). The fatty acids profile showed a relationship with the melting properties of dark chocolate. The samples exhibited two glass-transition temperatures (Tg) at ≈19 °C and ≈25.5 °C, possibly related to traces of unstable polymorphic forms of monounsaturated triacylglycerides. The analysis of bioactive compounds demonstrated great variability among samples independent of the cocoa origin, genotype, and content. The PCA and HCA Heatmaps allowed discriminating against the chocolates in relation to the cocoa origin and genotype. Compounds like tetramethylpyrazine, trimethylpyrazine, benzaldehyde, and furfural could be considered as dark-chocolate aroma markers derived from Latin American cocoas (North American region). The 2-phenylethyl alcohol, 2-methylpropanoic acid, 2,3-butanediol, 2-nonanone, and limonene for derived from South America. And the 2-phenylethyl acetate, 3-methyl-butanal, and cinnamaldehyde could allow to distinguishing between regional genotypes.

A distinctive epigenetic ageing profile in human granulosa cells.

STUDY QUESTION: Does women's age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells? SUMMARY ANSWER: Accumulation of epimutations by age and a higher number of age-related differentially methylated regions (DMR) in MGCs were found compared to leukocytes from the same woman, suggesting that the MGCs have a distinctive epigenetic profile. WHAT IS KNOWN ALREADY: The mechanisms underlying the decline in women's fertility from the mid-30s remain to be fully elucidated. The DNAm age of many healthy tissues changes predictably with and follows chronological age, but DNAm age in some reproductive tissues has been shown to depart from chronological age (older: endometrium; younger: cumulus cells, spermatozoa). STUDY DESIGN, SIZE, DURATION: This study is a multicenter cohort study based on retrospective analysis of prospectively collected data and material derived from healthy women undergoing IVF or ICSI treatment following ovarian stimulation with antagonist protocol. One hundred and nineteen women were included from September 2016 to June 2018 from four clinics in Denmark and Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples were obtained from 118 healthy women with varying ovarian reserve status. MGCs were collected from 63 of the 119 women by isolation from pooled follicles immediately after oocyte retrieval. DNA from leukocytes and MGCs was extracted and analysed with a genome-wide methylation array. Data from the methylation array were processed using the ENmix package. Subsequently, DNAm age was calculated using established and tailored age predictors and DMRs were analysed with the DMRcate package. MAIN RESULTS AND ROLE OF CHANCE: Using established age predictors, DNAm age in MGCs was found to be considerable younger and constant (average: 2.7 years) compared to chronological age (average: 33.9 years). A Granulosa Cell clock able to predict the age of both MGCs (average: 32.4 years) and leukocytes (average: 38.8 years) was successfully developed. MGCs differed from leukocytes in having a higher number of epimutations (P = 0.003) but predicted telomere lengths unaffected by age (Pearson's correlation coefficient = -0.1, P = 0.47). DMRs associated with age (age-DMRs) were identified in MGCs (n = 335) and in leukocytes (n = 1) with a significant enrichment in MGCs for genes involved in RNA processing (45 genes, P = 3.96 × 10-08) and gene expression (152 genes, P = 2.3 × 10-06). The top age-DMRs included the metastable epiallele VTRNA2-1, the DNAm regulator ZFP57 and the anti-Müllerian hormone (AMH) gene. The apparent discordance between different epigenetic measures of age in MGCs suggests that they reflect difference stages in the MGC life cycle. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: No gene expression data were available to associate with the epigenetic findings. The MGCs are collected during ovarian stimulation, which may influence DNAm; however, no correlation between FSH dose and number of epimutations was found. WIDER IMPLICATIONS OF THE FINDINGS: Our findings underline that the somatic compartment of the follicle follows a different methylation trajectory with age than other somatic cells. The higher number of epimutations and age-DMRs in MGCs suggest that their function is affected by age. STUDY FUNDING/COMPETING INTEREST(S): This project is part of ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS, the Danish National Research Foundation and the European Research Council. The authors declare no conflict of interest.

In silico analysis of antidiabetic potential of phenolic compounds from blue corn (Zea mays L.) and black bean (Phaseolus vulgaris L.).

The growing interest in bioactive compounds, especially in polyphenols, is due to their abundance in the human diet and potentially positive effects on health. The consumption of polyphenols has been shown to possess anti-diabetic properties by preventing insulin resistance or insulin secretion through different signaling pathways, this effect is associated with their capacity to exert genomic modulations. Several studies have suggested that polyphenols could also bind to cellular proteins and modulate their activity, however, the mechanisms of action underlying their beneficial effects are complex and are not fully understood. The aim of this work was to characterize phenolic compounds present in blue corn and black bean extracts as well as identify their potential interactions with target proteins involved in diabetes pathogenesis using in silico approach. Total polyphenols content of both blue corn and black beans was identified using UPLC-ESI/qTOF/MS and quantified by colorimetric assays. In this work we identified twenty-eight phenolic compounds in the extracts, mainly anthocyanins, flavonols, hydroxycinamic acids, dihydroxybenzoic acids, flavones, isoflavones, and flavanols. Interactome of these compounds with thirteen target proteins involved in type 2 diabetes mellitus was performed in-silico. In total, 312 bioactive compounds/protein interaction analyses were acquired. Molecular docking results highlighted that nine of the top ten interactions correspond to anthocyanins, cyanidin 3-glucoside with 11ß-HS, GFAT, PPARG; delphinidin 3-glucoside with 11ß-HS, GFAT, PTP and RTKs; and petunidin 3-glucoside with 11ß-HS and PTP. These proteins are involved in mechanisms regulating functions such as inflammation, insulin resistance, oxidative stress, glucose and lipid metabolism. In conclusion, this work provides a prediction of the potential molecular mechanism of black bean and blue corn polyphenols, specifically anthocyanins and could constitute new pathways by which compounds exert their antidiabetic benefits.

Efficacy of chemotherapy and atezolizumab in patients with non-small-cell lung cancer receiving antibiotics and proton pump inhibitors: pooled post hoc analyses of the OAK and POPLAR trials.

BACKGROUND: Preclinical data have shown that proton pump inhibitors (PPI) can modulate the microbiome, and single-arm studies suggested that antibiotics (ATB) may decrease the efficacy of immune checkpoint inhibitors (ICI), but randomized controlled trial data are lacking. This pooled analysis evaluated the effect of ATB and PPI on outcome in patients randomized between ICI and chemotherapy. PATIENTS AND METHODS: This retrospective analysis used pooled data from the phase II POPLAR (NCT01903993) and phase III OAK (NCT02008227) trials, which included 1512 patients with previously treated non-small-cell lung cancer (NSCLC) randomly assigned to receive atezolizumab (n = 757) or docetaxel (n = 755). The main objective of this analysis was to assess the impact of ATB and PPI use on overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 169 (22.3%) patients in the atezolizumab group and 202 (26.8%) in the docetaxel group received ATB, and 234 (30.9%) and 260 (34.4%), respectively, received PPI. Multivariate analysis in all patients revealed that ATB were associated with shorter OS [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], as was PPI (HR 1.26, 95% CI 1.10-1.44). Within the atezolizumab population, OS was significantly shorter in patients who received ATB (8.5 versus 14.1 months, HR 1.32, 95% CI 1.06-1.63, P = 0.01) or PPI (9.6 versus 14.5 months, HR 1.45, 95% CI 1.20-1.75, P = 0.0001). PPI use was associated with shorter PFS in the atezolizumab population (1.9 versus 2.8 months, HR 1.30, 95% CI 1.10-1.53, P = 0.001). There was no association between ATB and PPI use and PFS or OS within the docetaxel population. CONCLUSION: In this unplanned analysis from two randomized trials, data suggest that ATB or PPI use in patients with metastatic NSCLC is associated with poor outcome and may influence the efficacy of ICI.

EUS-guided tissue acquisition in the study of the adrenal glands: Results of a nationwide multicenter study.

BACKGROUND: There are limited data about the role of endoscopic ultrasound-guided tissue acquisition (EUS-TA), by fine needle aspiration (EUS-FNA) or biopsy (EUS-FNB), in the evaluation of the adrenal glands (AG). The primary aim was to assess the diagnostic yield and safety. The secondary aims were the malignancy predictors, and to create a predictive model of malignancy. METHODS: This was a retrospective nationwide study involving all Spanish hospitals experienced in EUS-TA of AGs. Inclusion period was from April-2003 to April-2016. Inclusion criteria: all consecutive cases that underwent EUS-TA of AGs. EUS and cytopathology findings were evaluated. Statistical analyses: diagnostic accuracy of echoendoscopist's suspicion using cytology by EUS-TA, as gold standard; multivariate logistic regression model to predict tumor malignancy. RESULTS: A total of 204 EUS-TA of AGs were evaluated. Primary tumor locations were lung70%, others19%, and unknown11%. AG samples were adequate for cytological diagnosis in 91%, and confirmed malignancy in 60%. Diagnostic accuracy of the endosonographer's suspicion was 68%. The most common technique was: a 22-G (65%) and cytological needle (75%) with suction-syringe (66%). No serious adverse events were described. The variables most associated with malignancy were size>30mm (OR2.27; 95%CI, 1.16-4.05), heterogeneous echo-pattern (OR2.11; 95%CI, 1.1-3.9), variegated AG shape (OR2.46; 95%CI, 1-6.24), and endosonographer suspicion (OR17.46; 95%CI, 6.2-58.5). The best variables for a predictive multivariate logistic model of malignancy were age, sex, echo-pattern, and AG-shape. CONCLUSIONS: EUS-TA of the AGs is a safe, minimally invasive procedure, allowing an excellent diagnostic yield. These results suggest the possibility of developing a pre-EUS procedure predictive malignancy model.

Real-world short-term effectiveness of ustekinumab in 305 patients with Crohn's disease: results from the ENEIDA registry.

BACKGROUND: There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM: To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS: Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (<250 µg/g) in 46% and 54% of the patients at weeks 8 and 14 respectively. CRP returned to normal (<3 mg/L) in the 35% and 41% of the patients at week 8 and 14 respectively. AEs were recorded in 38, and 40 patients were hospitalised. Intolerance to the most recent anti-TNF agent and fewer previous anti-TNF agents were associated with clinical remission at week 14. Endoscopic severity was associated with poor response. CONCLUSION: This is the first study to show the real-world effectiveness and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.

Titanium dioxide modified with silver by two methods for bactericidal applications.

"Titanium dioxide (TiO2) is a semiconductor material that exhibits antibacterial activity due to its photocatalytic properties under ultraviolet light. On the other hand, silver also exhibits strong antibacterial activity towards a wide range of microorganisms and TiO2 with silver addition exhibits more efficient photocatalytic properties than unmodified TiO2. In this work, TiO2 nanoparticles were synthesized by the hydrothermal method and modified with silver by two different methods: wet impregnation (Ex situ) and In situ incorporation. The antimicrobial activity of TiO2 nanoparticles synthesized and modified by both methods was evaluated against Escherichia coli and Staphylococcus aureus. The results showed that TiO2 nanoparticles have anatase phase. Also, spherical morphology with a mean particle size around 10.6 nm was obtained. The presence of silver in the modified TiO2 nanoparticles was confirmed by EDS and XPS. TiO2 particles modified by the Ex situ method, showed a better bactericidal activity compared to the particles modified by In situ incorporation method and TiO2 unmodified nanoparticles. This study demonstrated that both methods used to modify the titanium dioxide nanoparticles are effective as bactericidal materials and better results were found for the Ex situ method."

The health enhancer yeast Saccharomyces cerevisiae in two types of commercial products for animal nutrition.

The health enhancer yeast Saccharomyces cerevisiae (SC) is widely used in diets for different animals. Two main types of SC-based products are commercially available, one containing live yeasts and one containing SC fermentation by-products, which are supposedly not dependent on live yeasts for their physiological effects in vivo. Culture-based techniques were applied to study yeasts in two types of commercial products: a product containing live SC (LSC) and a SC fermentation product (SCFP). Three temperatures (25, 30 and 39°C) and two pH levels (4 and 7) were tested. The product with LSC contained an average of 1·21 × 109 colony-forming units (CFUs) of yeasts per g contents (min: 1 × 108 , max: 3 × 109 ). In contrast, the SCFP contained an average of 4·67 × 103 (min: 3 × 102 , max: 1·9 × 104 ) CFUs per g contents (c. 1 million times less than the concentration of yeasts in the product with LSC). Both temperature and pH level affected the number of CFUs but this effect differed between the two products. Biochemical tests identified the two yeasts as SC, which differed in their ability to ferment maltose (negative in the SCFP). This report encourages more research on commercial microbial strains for animal nutrition that can lead to a better understanding of their mode of action in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: Probiotics (or direct fed microbials) are increasingly popular in Animal Nutrition. Different products containing live micro-organisms or microbial-derived products are commercially available to enhance health and boost commercial traits. The characteristics of these products dictate their physiological effects and determine their potential to increase profitability from livestock. For the first time, this report presents data about the numbers and phenotype of the health enhancer Saccharomyces cerevisiae in two widely available commercial products in Animal Nutrition. These findings may be useful for scientists and producers around the globe and have the potential to open up novel venues for research.

A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma.

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.