Effectiveness and safety of vedolizumab in a matched cohort of elderly and nonelderly patients with inflammatory bowel disease: the IG-IBD LIVE study

Background Vedolizumab registration trials were the first to include elderly patients with moderate-to-severe ulcerative colitis (UC) or Crohn's disease (CD), but few real-life data have been reported in this population. Aims We investigated the effectiveness and safety of vedolizumab in matched cohorts of elderly and nonelderly UC and CD patients. Methods The Long-term Italian Vedolizumab Effectiveness (LIVE) study is a retrospective-prospective study including UC and CD patients who started vedolizumab from April 2016 to June 2017. Elderly patients (>= 65 years) were matched clinically 1:2 to nonelderly patients (18-64 years); the 2 groups were followed until drug discontinuation or June 2019. Results The study included 198 elderly (108 UC, 90 CD) and 396 matched nonelderly patients (205 UC, 191 CD). Nonelderly UC patients had a significantly higher persistence on vedolizumab compared to elderly patients (67.6% vs. 51.4%, p = 0.02). No significant difference in effectiveness was observed between elderly and nonelderly CD patients (59.4% vs. 52.4%, p = 0.32). Age >= 65 years was associated with lower persistence in UC; for CD, previous exposure to anti-TNF-alpha agents, Charlson comorbidity index >2 and moderate-to-severe clinical activity at baseline were associated with lower persistence. There were recorded 130 adverse events, with comparable rates between the two groups. A Charlson comorbidity index >2 was associated with an increased risk of adverse events. Conclusion Vedolizumab can be considered a safe option in elderly IBD patients. Its effectiveness in elderly UC patients may be reduced, while no age-dependent effect on effectiveness was observed in CD

A Triple and Quadruple Therapy with Doxycycline and Bismuth for First-Line Treatment of Helicobacter pylori Infection: A Pilot Study

Background: Tetracycline-containing triple therapy has been suggested as an alternative first-line therapy for H. pylori infection. Aim: To evaluate the effect of two dosages of doxycycline (DOX) associated with amoxicillin and esomeprazole with and without bismuth subcitrate as first-line treatment of H. pylori infection. Methods: Helicobacter pylori-positive patients underwent a 10-day therapy randomized into four groups: Group A received esomeprazole, amoxicillin, and DOX-100 mg b.i.d. (EAD-100), Group B a quadruple therapy with esomeprazole, amoxicillin, DOX-100 mg b.i.d. and bismuth subcitrate (EADB-100), Group C a triple therapy with esomeprazole, amoxicillin, and DOX-200 mg b.i.d. (EAD-200) and Group D a quadruple therapy with esomeprazole, amoxicillin, DOX-200 mg b.i.d., and bismuth subcitrate (EADB-200). Success was accessed by 13C urea breath test 2 months after the end of treatment. The number of patients to be recruited for each group had to be at least 50 subjects. Treatment success of 80% or less was considered unacceptable. Stopping rules therefore were anytime six failures had occurred. Results: In the EAD-100 group and in EAD-200 group, the recruitment was stopped at the 14th and 15th patient, respectively. Fifty-two patients entered in the EADB-100 group and 51 in the EADB-200 group. Intention to treat eradication was in EADB-100 group 46/52 (88.5%, 95% CI 76.6-95.6); in the EADB-200 group 47/51 (92.1%, 95% CI: 81.1-97.8) (n.s.). Side effects were absent. Conclusion: The adjunction of bismuth subcitrate to a triple therapy that includes esomeprazole, amoxicillin, and DOX in patients who are treated for the first time for the H. pylori infection potentiates the therapeutic effect. This regimen, however, deserves to be optimized in terms of duration and dose of DOX

Molecular pathways shared between host-parasitoid interaction in insect and other animals: The case of teratocyte extracellular enolase

Molecular pathways shared between host-parasitoid interaction in insect and other animals: The case of teratocyte extracellular enolase Introduction: Enolase is an ubiquitous metalloenzyme involved in the glycolytic pathway. Interestingly it appears also as a multifunctional protein. Enolases anchored on the outer surface of the plasma membrane are involved in tissue invasion mechanisms by the activation of Plasminogen. Methods: To determine the Enolase localization and its capacity to bind and activate the plasminogen, experiments of immunogold labeling, indirect immunofluorescence staining, co-localization, binding and activation in vitro assay, Duolink in situ Proximity Ligation Assay (PLA) and dot blotting assay were carried out. Furthermore the Enolase ability to degrade extracellular matrix was in vitro evaluated by a Matrix digestion assay. Results/Conclusion: We have identified an extracellular Enolase (Ae-ENO) produced by teratocytes, embryonic cells of the insect parasitoid Aphidius ervi (Hymenoptera, Braconidae). For the first time we demonstrate that Ae-ENO, although lacking a signal peptide, accumulates in cytoplasmic vesicles oriented towards the cell membrane. Ae-ENO binds and activates a plasminogen-like molecule inducing digestion of the host tissue and thereby ensuring successful parasitism. The results support the hypothesis of the existence of plasminogen-like proteins in invertebrates and their activation through mechanisms involving the surface enolase/fibrinolytic system that until now seemed to be exclusively found in vertebrates, and that is conserved across species. These findings also suggest that Ae-ENO is a novel and unique example of gene sharing in insects

The effect of Leptomastix dactylopii parasitism and venom injection on host Planococcus citri

10One of the major alterations observed in mealybug Planococcus citri parasitized by Leptomastix dactylopii is a strong reduction of laid eggs, which is evident soon after parasitization. Venom injection in unparasitized hosts determines a drastic reduction of fecundity indicating that this female secretion injected at the oviposition plays a key-role in host regulation. In order to assess the impact of parasitism and venom injection on host reproductive tissues, ovaries were dissected at different time intervals after these treatments and observed by light and transmission electron microscopy. The developing eggs showed clear symptoms of degeneration, already half an hour after parasitization or venom injection. Heat and protease treatments of venom nearly suppressed its effects on host reproduction, indicating that proteins are likely responsible for the observed alterations. The electrophoretic profile of venom proteins covers a wide range of molecular masses between 15 to 200 kDa but five major bands having a molecular mass of about 27, 30, 40, 90 and 120 kDa respectively were more evident. Moreover, to establish any parasitoid preference in host selection, among the adult female mealybugs at different stages of maturation and a possible relation with fecundity reduction in the host, the parasitoid behavior was observed.openBattaglia, D.; Colella, T.; Laurino, S.; Grossi, G.; Salvia, R.; Riviello, L.; Grimaldi, A.; Congiu, T.; de Eguileor, M.; Falabella, P.Battaglia, D.; Colella, T.; Laurino, S.; Grossi, G.; Salvia, R.; Riviello, L.; Grimaldi, Annalisa; Congiu, Terenzio; DE EGUILEOR, MAGDA ANNA; Falabella, P

XXV CONGRESSO NAZIONALE ITALIANO DI ENTOMOLOGIA

L’enolasi extracellulare dei teratociti di Aphidius ervi (Ae-ENO) lega e attiva una proteina Plasminogen-like inducendo la degradazione della matrice extracellulare. Lo studio delle basi molecolari delle interazioni ospite-parassitoide nel sistema biologico Acyrthosiphon pisum / Aphidius ervi ha consentito di identificare i fattori parassitari di origine materna ed embrionale, che svolgono un ruolo importante nella regolazione dell’ospite. I teratociti, cellule derivanti dalla dissociazione della serosa embrionale del parassitoide, sono responsabili di una digestione extra-orale dei tessuti dell’ospite al fine di trasformarli in un substrato immediatamente disponibile per la progenie. Sono cellule che crescono rapidamente in dimensione, diventando altamente poliploidi, e il loro ruolo di supporto nutrizionale alla larva è sostenuto dalla capacità di sintetizzare e rilasciare nell’emolinfa in particolare due proteine: una Fatty Acid Binding Protein (Ae-FABP), che media il trasporto di acidi grassi nell’emolinfa dell’ospite per renderli disponibili alla larva, e una Enolasi (Ae-ENO). Quest’ultima, oltre alla normale attività di enzima glicolitico, è anche espressa sulla superficie esterna dei teratociti, sebbene la sua sequenza amminoacidica manchi del peptide segnale. Esperimenti di Immunogold labeling e Microscopia Elettronica a Trasmissione (TEM) hanno dimostrato che il trasporto dell’Ae-ENO verso la superficie dei teratociti potrebbe essere mediato da strutture esosoma-like, analogamente a quanto osservato in molti altri organismi eucarioti e procarioti. L’Ae-ENO localizzata sulla superficie cellulare dei teratociti funge da recettore di una proteina plasminogen-like presente nell’emolinfa dell’ospite A. pisum, trasformandola nella forma attiva, plasmina, responsabile della degradazione della matrice extracellulare (ECM) dell’ospite stesso. Esperimenti condotti in vitro hanno mostrato, infatti, che Ae-ENO presente sulla superficie dei teratociti interagisce con il plasminogeno umano attivandolo in plasmina in presenza del corrispondente attivatore uPA (Urokinase Plasminogen Activator). Inoltre, teratociti incubati con plasminogeno umano e uPA seminati su un supporto ECM-like, hanno dimostrato la loro capacità in vitro di degradazione della matrice extracellulare. Questi risultati supportano l'ipotesi dell’esistenza di proteine plasminogen-like negli invertebrati, la cui attivazione è mediata da un meccanismo che coinvolge una enolase extracellulare fino ad ora considerato esclusivo dei vertebrati, e che invece risulta essere conservato tra le specie. Si tratta quindi della prima dimostrazione di un processo di degradazione della ECM mediato dalla attivazione di una proteina Plasminogen-like presente nell’insetto ospite

Rifabutin Containing Triple Therapy and Rifabutin with Bismuth Containing Quadruple Therapy for Third-Line Treatment of Helicobacter pylori Infection: Two Pilot Studies

Aim: To evaluate the therapeutic gain of the addition of bismuth to a rifabutin containing triple therapy with amoxicillin and pantoprazole at standard dosages for the treatment of third-line Helicobacter pylori infection after a preliminary susceptibility test. Methods: Two separate groups of patients in two pilot studies which were carried out simultaneously. One group was treated with rifabutin 150 mg b.i.d., pantoprazole 20 mg b.i.d., and amoxicillin 1 g b.i.d. for 10 days and the other group with rifabutin 150 mg b.i.d., pantoprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and bismuth subcitrate 240 mg b.i.d. for 10 days. All patients underwent to culture and susceptibility testing prior to their inclusion in the study. A successful outcome was confirmed with an Urea Breath test performed 8 weeks after the end of treatment. A blood cell count was performed for all patients at the start and after 5 days of treatment since rifabutin has been shown to inhibit the growth of leucocytes. Results: Twenty-nine patients were recruited in the pantoprazole, amoxicillin, rifabutin group and 30 in the pantoprazole, amoxicillin, rifabutin, and bismuth subcitrate group. All patients had a positive H. pylori culture and the susceptibility test used showed H. pylori sensitivity to rifabutin and amoxicillin. H. pylori eradication during follow-up was 18/27 (66.7%, 95% CI: 47.7–85.7%) in the pantoprazole, amoxicillin, rifabutin group and 28/29 (96.6%, 95% CI: 89.5–100.0%) in the pantoprazole, amoxicillin, rifabutin, and bismuth subcitrate group. Both treatments were well-tolerated with no reported side effects. Blood cell count remained normal in all patients. Conclusion: The addition of bismuth subcitrate to a triple therapy that includes proton pump inhibitors, amoxicillin, and rifabutin in patients who are treated for the third time for H. pylori infection resulted in a 30% therapeutic gain

Disease activity and health-related quality of life in inflammatory bowel disease patients during outbreak of COVID-19

The present study aimed to investigate the extent to which health-related quality of life of patients with inflammatory bowel disease (IBD) was influenced by the outbreak of Covid-19 while controlling for disease activity. Two samples of 195 (recruited before Covid-19 outbreak) and 707 patients (recruited during the Covid-19-related lockdown) were included. Psychological distress (Hospital Anxiety and Depression Scale, HADS), quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), and somatization (Patient Health Questionnaire, PHQ-12) were concurrently assessed. Patients with active IBD were more prevalently affected by ulcerative colitis (60.2%) and, expectedly, showed higher psychological distress (HADS, d = 0.34) and somatization (PHQ-12, d = 0.39), as well as poorer disease-specific health-related quality of life (effect sizes for the total and subscale IBDQ scores in the large range of d > 0.50). Hierarchical regression models revealed that setting (pre-Covid-19 outbreak vs. during lockdown) (p < 0.001) explained only a small portion (8%) of the IBDQ variance. IBD-related factors (ulcerative colitis and disease activity) and psychological factors (psychological distress and somatization) added a significant amount of 25 and 27%, respectively, to the explained IBDQ variance. The final model predicted 59% of the explained IBDQ variance. Clinical and psychological manifestations seem to be major impairments in IBD patients both before and during the Covid-19 outbreak. Furthermore, the quality of life of IBD patients seem to be more influenced by psychological and somatizing distressing symptoms than the pandemic-related living conditions

Influence of the COVID-19 Outbreak on Disease Activity and Quality of Life in Inflammatory Bowel Disease Patients

Objective: The present preliminary cross-sectional study aimed to investigate the extent to which health-related quality of life of patients with inflammatory bowel disease (IBD) was influenced by the outbreak of Covid-19 while controlling for disease activity. Methods: Two samples of 195 (recruited before Covid-19 outbreak) and 707 patients (recruited during the Covid-19-related lockdown) were included. Psychological distress (Hospital Anxiety and Depression Scale, HADS), quality of life (Inflammatory Bowel Disease Questionnaire, IBDQ), and somatization (Patient Health Questionnaire, PHQ-12) were concurrently assessed. Results: Patients with active IBD were more prevalently affected by ulcerative colitis (60.2%, !2 = 0.12) and, expectedly, showed higher psychological distress (HADS, d = 0.34) and somatization (PHQ-12, d = 0.39), as well as poorer disease-specific health-related quality of life (effect sizes for the total and subscale IBDQ scores in the large range of d > 0.50). Hierarchical regression models revealed that setting (pre-Covid-19 outbreak vs. during lockdown) (p < 0.001) explained only a small portion (8%) of the IBDQ variance. IBD-related factors (ulcerative colitis and disease activity) and psychological factors (psychological distress and somatization) added a significant amount of 25 and 27%, respectively, to the explained IBDQ variance. The final model predicted 59% of the explained IBDQ variance. Conclusion: Clinical and psychological manifestations seem to be major impairments in IBD patients both before and during the Covid-19 outbreak. Furthermore, the quality of life of IBD patients seem to be more influenced by psychological and somatizing distressing symptoms than the pandemic-related living conditions