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Background: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. Methods: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). Results: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (16 8.5) and w4 8 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48.Conclusions: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.(c) 2023 The Authors. Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

BACKGROUND: Dengue can be complicated by severe outcomes including cardiac impairment, and the lack of reliable prognostic biomarkers poses a challenge in managing febrile dengue patients. Here, we investigated the functionality of soluble suppressor of tumorigenicity (sST2) as a predictive marker of severe dengue and its association in dengue-associated cardiac impairment. METHODS: Plasma samples, aged >16 years, collected from 36 dengue fever, 43 dengue with warning signs, 11 severe dengue (collected at febrile, critical and recovery phases) and 30 controls were assayed for plasma levels of sST2, troponin T and N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) by ELISA. Cardiac parameters: stroke index (SI), cardiac index (CI) and Granov-Goor Index (GGI) were measured with a bioimpedance device during the different phases for dengue subjects and once for the controls. PRINCIPAL FINDINGS: In the febrile, critical and early recovery phases, sST2 levels were significantly elevated in dengue participants and sST2 levels increased with increasing disease severity (P < 0.01 for all). sST2 concentrations were negatively correlated with SI (r = -0.48; P < 0.001, r = -0.55; P < 0.001), CI (r = -0.26; P = 0.02, r = -0.6: P < 0.001) and GGI (r = -0.44; P < 0.001, r = -0.57; P < 0.001) in the critical and early recovery phases. In contrast, sST2 levels in the febrile and critical phases, were positive correlated to troponin T (r = 0.44, P < 0.001; r = 0.22, P = 0.03, respectively) and NT-proBNP (r = 0.21, P = 0.03; r = 0.35, P < 0.001). ROC analysis demonstrated sST2 as a good biomarker of severe dengue in the critical phase, AUROC 0.79, P < 0.001. CONCLUSION/SIGNIFICANCE: sST2 levels were elevated in patients with dengue especially in cases of severe dengue. Furthermore, increased sST2 levels were associated with cardiac indicators suggesting lower cardiac performance. While further research is needed to demonstrate its clinical utility, sST2 may be a useful

Background: Older age and comorbidities are the main risk factors for adverse COVID-19 outcomes in patients with inflammatory bowel disease (IBD). The impact of IBD medications is still under investigation. Aims: To assess risk factors for adverse outcomes of COVID-19 in IBD patients and use the identified risk factors to build risk indices. Methods: Observational cohort study. Univariable and multivariable logistic regression was used to identify risk factors associated with pneumonia, hospitalisation, need for ventilatory support, and death. Results: Of the 937 patients (446 with ulcerative colitis [UC]) evaluated, 128 (13.7%) had asymptomatic SARS-CoV-2 infection, 664 (70.8%) had a favourable course, and 135 (15.5%) had moderate or severe COVID-19. In UC patients, obesity, active disease and comorbidities were significantly associated with adverse outcomes. In patients with Crohn's disease (CD), age, obesity, comorbidities and an additional immune-mediated inflammatory disease were identified as risk factors. These risk factors were incorporated into two indices to identify patients with UC or CD with a higher risk of adverse COVID-19 outcomes. In multivariable analyses, no single IBD medication was associated with poor COVID-19 outcomes, but anti-TNF agents were associated with a lower risk of pneumonia in UC, and lower risks of hospitalisation and severe COVID-19 in CD. Conclusion: The course of COVID-19 in patients with IBD is similar to that in the general population. IBD patients with active disease and comorbidities are at greater risk of adverse COVID-19 outcomes. IBD medications do not pose additional risks. The risk indices may help to identify patients who should be prioritised for COVID-19 re-vaccination or for therapies for SARS-CoV-2 infection.

Background: Efficacy and safety of ustekinumab for the treatment of ulcerative colitis (UC) has been demonstrated in clinical trials, but few real-world data are available so far. The aim of this study was to assess effectiveness and safety of ustekinumab in a cohort of refractory UC patients. Methods: Data of patients with moderate to severe UC treated with ustekinumab were retrospectively collected. Primary endpoint was steroid-free clinical remission at weeks 24 and 52 of therapy. Secondary endpoints were treatment response, endoscopic remission, treatment persistence at 12 months and safety. Results: A total of 68 patients [males 63%; median (range) age 42 (16–72) years] were included. Almost all patients (97%) were biologics experienced. At weeks 24 and 52, 31% and 50% of patients achieved steroid-free clinical remission, 84% and 82% had clinical response, respectively. At the end of follow-up, there was a significant reduction of pMS from baseline (p < 0.001) and of steroid use (p < 0.001). At week 52, 22% of the available endoscopies (18/38) showed mucosal healing. The probability to persist in therapy at week 52 was 87%. Only one adverse event occurred. Conclusions: Data from our real-life cohort of refractory UC patients suggest satisfactory effectiveness and a good safety of ustekinumab.

Ascaris is a soil-transmitted nematode that causes ascariasis, a neglected tropical disease affecting predominantly children and adolescents in the tropics and subtropics. Approximately 0.8 billion people are affected worldwide, equating to 0.86 million disability-adjusted life-years (DALYs). Exploring the molecular biology of Ascaris is important to gain a better understanding of the host-parasite interactions and disease processes, and supports the development of novel interventions. Although advances have been made in the genomics, transcriptomics and proteomics of Ascaris, its lipidome has received very limited attention. Lipidomics is an important sub-discipline of systems biology, focused on exploring lipids profiles in tissues and cells, and elucidating their biological and metabolic roles. Here, we characterised the lipidomes of key developmental stages and organ systems of Ascaris of porcine origin via high throughput LC-MS/MS. In total, > 500 lipid species belonging to 18 lipid classes within three lipid categories were identified and quantified–in precise molar amounts in relation to the dry weight of worm material–in different developmental stages/sexes and organ systems. The results showed substantial differences in the composition and abundance of lipids with key roles in cellular processes and functions (e.g. energy storage regulation and membrane structure) among distinct stages and among organ systems, likely reflecting differing demands for lipids, depending on stage of growth and development as well as the need to adapt to constantly changing environments within and outside of the host animal. This work provides the first step toward understanding the biology of lipids in Ascaris, with possibilities to work toward designing new interventions against ascariasis.

Background: We report a prospective, nationwide cohort evaluating the safety and effectiveness of CT-P13. Methods: A structured database was used to record serious adverse events (SAEs), clinical remission/response, inflammatory biomarkers (CRP and calprotectin), and endoscopic findings. Results: Eight hundred ten patients with inflammatory bowel disease (IBD) (452 Crohn's disease [CD]) were enrolled. Four hundred fifty-nine patients were naïve to anti-TNFα (group A), 196 had a previous exposure (group B), and the remaining 155 were switched to CT-P13 (group C). All patients were included in the safety evaluation with a mean follow-up of 345 ± 215 days and a total number of 6501 infusions. One hundred fifty-four SAEs were reported (19%), leading to cessation of the biosimilar in 103 subjects (12.7%). Infusion reactions were 71, leading to cessation of the biosimilar in 53 subjects (6.5%), being significantly more frequent in patients pre-exposed to anti-TNFα (P = 0.017). The efficacy of therapy was calculated in 754 IBD patients, with a mean follow-up of 329 ± 202 days. Forty-eight patients had a primary failure (6.4%), and 188 (25.6%) lost response during follow-up. Six hundred twenty-eight (364 CD) and 360 IBD patients (222 CD) completed the follow-up at 6 and 12 months, respectively. At 12 months, patients without loss of response were 71%, 64%. and 82% in groups A, B, and C, respectively (log rank P = 0.01). Clinical/endoscopic scores and inflammatory biomarkers dropped significantly in CD and UC patients (P = 0.01 and P < 0.0001) compared with baseline. Conclusions: In this large prospective cohort, no further signals of difference in safety and effectiveness of CT-P13 in IBD has been observed.

We examined faecal egg count reduction tests (FECRTs) conducted with hookworm-infected humans in Ghana in 2007 (study 1) and 2010 (study 2) in order to explore aspects of the test analysis. Some subjects showed increased FEC following drug treatment. This occurred mostly in <150. epg pre-treatment FEC subjects. We sought a means to remove 'erroneous' negative drug efficacy cases from the FECRT analysis. Pre- and post-treatment FECs from negative drug efficacy cases were examined to determine whether they represented replicates from a single randomly distributed sample, that is, if they were consistent with a Poisson distribution. Cases where the post-treatment FEC was greater than that expected if it and the pre-treatment sample had been taken from a single random distribution of eggs were excluded from the FECRT. We suggest that these cases most likely represent non-random distribution of eggs in stools, day-to-day variations in egg excretion, or worm patency onset after drug treatment, and hence are not accurate measurements of drug efficacy. This led to exclusion of the most extreme negative drug efficacy cases, with significant increases in overall drug efficacy for study 1 (81.6% vs 89.2%) and study 2 (86.7% vs 89.4%). Excluding FEC <150 individuals from the analysis also increased the study 1 efficacy (81.6% vs 88.9%), however, this resulted in the exclusion of 45% of the study subjects, compared to the exclusion of just 5% using the Poisson distribution method. While low FEC subjects are excluded from livestock FECRTs, the significant prevalence of such subjects in human FECRTs suggests that their exclusion may not be practical. Hence, we suggest that the influence of low FECs can be minimised by excluding 'erroneous' negative efficacy cases using a simple Poisson distribution analysis.

We examined faecal egg count reduction tests (FECRTs) conducted with hookworm-infected humans in Ghana in 2007 (study 1) and 2010 (study 2) in order to explore aspects of the test analysis. Some subjects showed increased FEC following drug treatment. This occurred mostly in <150. epg pre-treatment FEC subjects. We sought a means to remove 'erroneous' negative drug efficacy cases from the FECRT analysis. Pre- and post-treatment FECs from negative drug efficacy cases were examined to determine whether they represented replicates from a single randomly distributed sample, that is, if they were consistent with a Poisson distribution. Cases where the post-treatment FEC was greater than that expected if it and the pre-treatment sample had been taken from a single random distribution of eggs were excluded from the FECRT. We suggest that these cases most likely represent non-random distribution of eggs in stools, day-to-day variations in egg excretion, or worm patency onset after drug treatment, and hence are not accurate measurements of drug efficacy. This led to exclusion of the most extreme negative drug efficacy cases, with significant increases in overall drug efficacy for study 1 (81.6% vs 89.2%) and study 2 (86.7% vs 89.4%). Excluding FEC <150 individuals from the analysis also increased the study 1 efficacy (81.6% vs 88.9%), however, this resulted in the exclusion of 45% of the study subjects, compared to the exclusion of just 5% using the Poisson distribution method. While low FEC subjects are excluded from livestock FECRTs, the significant prevalence of such subjects in human FECRTs suggests that their exclusion may not be practical. Hence, we suggest that the influence of low FECs can be minimised by excluding 'erroneous' negative efficacy cases using a simple Poisson distribution analysis.

The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres.

We report a case of a 42-year-old man with a right pleural mesothelioma. This neoplasm has 3 rare features. Firstly, it was a localized form: suspected by imaging, visualized by video-assisted thoracoscopy, at the time of the curative-thoracotomy and confirmed by the pathological analysis. The second characteristic is its histological type: "malignant lymphohistiocytoid mesothelioma". This rare subtype has been reported in only 4 papers. Third, after pleuro-pneumonectomy, our patient is alive after 6 years and 5 months postoperatively without any sign of recurrence. Only one case with a long follow-up has been reported but with recurrence at 5 years postoperatively.

Respiratory symptoms are rare manifestations of ulcerative colitis as well as intestinal manifestations in Wegener granulomatosis. We report the case of a 17-year old man previously diagnosed as having ulcerative colitis who presented with diffuse thoracic pain. Hypermetabolic pulmonary nodules were discovered at the positron emission tomographic scan. Necrotizing granulomatous vasculitis was demonstrated at lung biopsy. In this paper, we describe the association between pulmonary nodules and ulcerative colitis and we discuss the possibility of an overlap syndrome between ulcerative colitis and Wegener granulomatosis.

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to 'biological process' (n = 68), 'cellular component' (n = 50), or 'molecular function' (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein-protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arr

BACKGROUND: Parasitic nematodes of humans, other animals and plants continue to impose a significant public health and economic burden worldwide, due to the diseases they cause. Promising antiparasitic drug and vaccine candidates have been discovered from excreted or secreted (ES) proteins released from the parasite and exposed to the immune system of the host. Mining the entire expressed sequence tag (EST) data available from parasitic nematodes represents an approach to discover such ES targets. METHODS AND FINDINGS: In this study, we predicted, using EST2Secretome, a novel, high-throughput, computational workflow system, 4,710 ES proteins from 452,134 ESTs derived from 39 different species of nematodes, parasitic in animals (including humans) or plants. In total, 2,632, 786, and 1,292 ES proteins were predicted for animal-, human-, and plant-parasitic nematodes. Subsequently, we systematically analysed ES proteins using computational methods. Of these 4,710 proteins, 2,490 (52.8%) had orthologues in Caenorhabditis elegans, whereas 621 (13.8%) appeared to be novel, currently having no significant match to any molecule available in public databases. Of the C. elegans homologues, 267 had strong "loss-of-function" phenotypes by RNA interference (RNAi) in this nematode. We could functionally classify 1,948 (41.3%) sequences using the Gene Ontology (GO) terms, establish pathway associations for 573 (12.2%) sequences using Kyoto Encyclopaedia of Genes and Genomes (KEGG), and identify protein interaction partners for 1,774 (37.6%) molecules. We also mapped 758 (16.1%) proteins to protein domains including the nematode-specific protein family "transthyretin-like" and "chromadorea ALT," considered as vaccine candidates against filariasis in humans. CONCLUSIONS: We report the large-scale analysis of ES proteins inferred from EST data for a range of parasitic nematodes. This set of ES proteins provides an inventory of known and novel members of ES proteins as a foundation fo