Post-Covid-19 Irritable Bowel Syndrome

Background and aim: The long-term consequences of COVID- 19 infection on the gastrointestinal tract remain unclear. Here we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction (DGBI) after hospitalization for SARS-CoV-2 infection. Material(s) and Method(s): GI-COVID19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were evaluated upon hospital admission and after 1, 6, and 12 months post-hospitalization. Gastrointestinal symptoms, anxiety, and depression were assessed using validated questionnaires, namely the Gastrointestinal Symptoms Rating Scale (GSRS), the Hanxiety and Depression Scale (HADS) and the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults. Result(s): The study included 2183 hospitalized patients. The primary analysis included a total of 883 patients (614 COVID-19 patients and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrollment, gastrointestinal symptoms were more frequent among COVID-19 patients than in the control group (59.3% vs. 39.7%, P<0.001). At the 12-month follow- up, constipation and hard stools were significantly more prevalent in controls than in COVID-19 patients (16% vs. 9.6%, P=0.019 and 17.7% vs. 10.9%, P=0.011, respectively). Compared to controls, COVID- 19 patients reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% vs. 3.2%, P=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors, and presence of dyspnea. [Table presented] At the 6-month follow-up, the rate of COVID-19 patients fulfilling the criteria for depression was higher than among controls. Conclusion(s): Compared to controls, hospitalized COVID-19 patients had fewer complaints of constipation and hard stools at 12 months after acute infection. COVID-19 patients had significantly higher rates of IBS than controls. ClinicalTrials.gov number, NCT04691895.Copyright © 2023. Editrice Gastroenterologica Italiana S.r.l.

Genomic profiling of primary and recurrent ovarian cancers: A retrospective single-center experience

Background: The oncology landscape is rapidly evolving towards more personalized treatment with the use of molecular-driven therapies. Thus, genomic information has become an integral component of clinical decision-making. This study aims to analyze tumor tissue samples of high-grade serous ovarian cancer (HGSOC) to understand if genomic changes in gene mutation frequencies between primary and relapsing tumors occur and can influence the detection of actionable gene alterations. Method(s): A retrospective study approved by local Ethics Committee was conducted on OC patients treated at Fondazione Policlinico Universitario A. Gemelli, IRCCS. All subjects provided informed written consent for genetic analysis and study participation. FFPE specimens were analyzed by Foundation One CDx, which applies NGS across 324 genes known to be drivers of solid tumors, by sequencing the coding regions of 309 cancer-related genes plus introns from 36 genes. Z-test was used to analyze the mutation frequencies between primary and relapsing tumors. Result(s): 261 patients underwent Foundation Medicine testing. Out of 216 HGSOC, 151 tests were performed on primary lesion, 43 at 1st/2nd recurrence, and 22 at >3 recurrences. Statistically significant changes in BRCA1-2 frequencies were found between primitive lesions and recurrence (p=0.0013). A lower frequency in TP53 (p=0.0013) and a higher frequency of NF1 (p=0.028) and TERC (p=0.027) mutations were shown in tissue collected at recurrence compared to primary lesion. Selective chemotherapy pressure and natural enrichment of better prognosis patients at recurrence may explain the discrepancies between primary and secondary tumors. Conclusion(s): These data suggest the opportunity to re-characterize the molecular profiling of the tumors at the time of recurrence to identify potentially actionable alterations to guide treatment. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electric fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Persona , Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD;Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono;Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro;Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar;Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD;Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen;Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche;Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK;Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, GenMab;Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, clovis, Incyte;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche;Non-Financial Interests, P rsonal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

Clinical relevance of NGS analysis in endometrial cancer (EC) management

Background: After the introduction of the molecular classification in EC guidelines, Next Generation Sequencing (NGS) analysis has become an essential tool for EC management. Molecular-driven therapies have also been recently tested, and some have obtained FDA approval. This retrospective cohort study aims to determine the clinical benefit rate (CBR) with the use of targeted therapies based on NGS in ECs patients. Method(s): After approval of the local Ethics Committee, a retrospective study was conducted on EC patients undergoing Foundation Medicine testing at Fondazione Policlinico Universitario Agostino Gemelli IRCCS. All patients provided written informed consent. Formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens were analyzed by Foundation One CDx, which detects 324 genes known to be drivers of solid tumors based on NGS assay. Efficacy outcomes were estimated by the Kaplan-Meier method and expressed as median with its 95% confidence interval. IBM-SPSS v.27.0 software was used for statistical analyses. Result(s): Out of 35 tests performed, 11 patients received a targeted therapy based on actionable mutations detected with the NGS assays. All the 11 patients had been heavily pretreated (>=3 prior lines). One patient died because of COVID-19 and thus was excluded from the analysis. Out of the 10 patients included, targeted therapies showed an overall CBR of 80% in 8 patients (10% CR, 33.3% PR, 40% SD, and 20% PD). 7 patients were treated with a targeted agent belonging to the PI3K pathway, with 3 PR (42.9%), 3 SD (42.9%), and 1 PD (14.2%). 3 patients received PARP inhibitor treatment according to their HRD status, with 1 CR (33.3%), 1 SD (33.3%), and 1 PD (33.3%). Conclusion(s): In our series, an outstanding CBR of 80% was achieved with the use of targeted therapy according to NGS assays in heavily pretreated patients (>=3 prior lines). Our finding underlines the importance of molecular-driven treatments and requires further investigation to confirm these results in terms of clinical benefit in a broader population. Besides, the use of molecular-driven treatments may avoid unnecessary exposure to potentially more toxic therapies and reduce the costs associated with inappropriate treatments. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: V. Salutari: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Clovis, GSK, Tesaro, MSD, Roche, PharmaMar, Eisai. G. Scambia: Financial Interests, Personal, Invited Speaker, Speaker: Johnson & Johnson, AstraZeneca & MSD, Olympus Europa, Baxter Healthcare, Intuitive Surgical Inc., GlaxoSmithKline;Financial Interests, Personal, Expert Testimony, Trainer: Covidien AG (Medtronic company);Financial Interests, Institutional, Invited Speaker, 'IsoMSLN' in Ovarian Cancer and Malignant Pleural Mesothelioma: Kiromic;Financial Interests, Institutional, Invited Speaker, Roll-over study for patients who have completed a previous cancer study with olaparib and who the investigator believes can benefit from continued treatment - ROSY-O: AstraZeneca;Financial Interests, Institutional, Invited Speaker, CATCH-R: Roll-over study to provide continuous access to clinical therapy with rucaparib: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, Phase III, multicenter, placebo-controlled clinical study comparing chemo-immunotherapy (paclitaxel-carboplatin-oregovomab) versus chemotherapy (paclitaxel-carboplatin-placebo) in patients with advanced epithelial ovarian, tubal cancer of fallopian or peritoneal (FLORA-5): Oncoquest Pharmaceuticals Inc.;Financial Interests, Institutional, Invited Speaker, Phase IIb randomized, open-label, active comparator, parallel-group, multicenter study designed to evaluate the efficacy and safety of three different doses of the P2X3 receptor antagonist (BAY 1817080) versus placebo and Elagolix 150 mg in women with symptomatic endometriosis: Bayer AG;Financial Interests, Institutional, Invited Speaker, Usability of ITE transducers for sending electr c fields for tumor treatment (TTFields): Novocure Ltd.;Financial Interests, Institutional, Invited Speaker, Phase III, multicentre, open-label extension trial to evaluate long-term safety and efficacy in patients with advanced cancers currently undergoing treatment or in follow-up in a pembrolizumab trial: Merck. D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD;Financial Interests, Personal, Other, Consultancy: PharmaMar, Amgen, AstraZeneca, Clovis Oncology, GSK, MSD, Immunogen, Genmab, Seagen;Financial Interests, Personal, Advisory Board, Participation in Advisory Boards: Merck Serono;Financial Interests, Personal, Advisory Board, Invited member of advisory board: Seagen, Immunogen, Genmab, Oncoinvest, Corcept, Sutro;Financial Interests, Institutional, Funding, Grant for founding academic trial: MSD, Clovis Oncology, PharmaMar;Financial Interests, Institutional, Funding, Grant for founding academic trial: GSK;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Clovis Oncology;Financial Interests, Institutional, Invited Speaker, ENGOT trial with institutional support for coordination: Genmab, MSD;Financial Interests, Institutional, Funding, Clinical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen;Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, Immunogen, Incyte, Novartis, Roche;Non-Financial Interests, Personal, Principal Investigator, PI of several trials, no compensation received: GSK;Non-Financial Interests, Personal, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, Genmab;Non-Financial Interests, Personal, Principal Investigator, PI in several trials. No personal compensation received: MSD;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation received: Immunogen, Clovis, Incyte;Non-Financial Interests, Personal, Principal Investigator, PI of clinical trial. No personal compensation receive: Roche;Non-Financial Int rests, Personal, Member, Board of Directors: GCIG. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology

Post-Infection Irritable Bowel Syndrome in Sars-Cov-2 Patients: The Gi-Covid19 Study

Introduction: SARS-CoV-2 infection, known as COVID-19, may lead to persistent gastrointestinal dysfunction resembling aspects of post-infection disorders of gut-brain interaction (DGBI). However, the long-term consequences of COVID-19 on the gastrointestinal tract remain unclear. Aims & Methods: We aimed to evaluate the prevalence of gastrointestinal symptoms and post-infection disorders of gut-brain interaction (DGBI) up to 12 months after hospitalization and the factors associated with their presence. The GI-COVID19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were assessed at hospital admission and followed up after 1, 6, and 12 months to assess gastrointestinal symptoms using the Gastrointestinal Symptoms Rating Scale, the Rome IV Diagnostic Questionnaire for Functional Gastrointestinal Disorders in Adults, and the hospital anxiety and depression scale. ClinicalTrials. gov number, NCT04691895. Result(s): The study included2183 hospitalized patients. After excluding patients with pre-existing gastrointestinal symptoms and/or surgery, a total of 883 patients (614 COVID-19 and 269 controls) were included in the primary analysis, of whom 435 COVID-19 and 188 controls completed 12 months of follow-up. At enrollment, gastrointestinal symptoms occurred more frequently in COVID-19 patients than in the control group (59.3% vs. 39.7%, P<0.001). Symptoms more frequently complained by COVID-19 patients at enrollment were nausea, diarrhea, loose stool, and urgency. At 1-month follow-up evaluation, nausea and acid regurgitation were significantly more prevalent in COVID-19 patients than in the control group (8.7% vs. 1.7%, P=0.015 and 8.4% vs. 2.1%, P=0.006, respectively). At 6 months, COVID-19 patients reported lower rates of flatus (17.6% vs. 19.1%, P=0.024), constipation (8.9% vs. 17.1%, P<0.001) and hard stools (9.6 vs. 17.2%, P=0.030) as compared with the control group. At 12 months, constipation and hard stools were significantly less prevalent in COVID-19 patients than in the control group (9.6% vs. 16%, P=0.019 and 10.9% vs. 17.7%, P=0.011, respectively). COVID-19 patients reported higher rates of DGBI during follow-up compared to controls (Table), although statistically significant differences were found only for irritable bowel syndrome (IBS) according to Rome III criteria (4.4% vs 1.1%, P=0.036) and Rome IV criteria (3.2% vs 0.5%, P=0.045). The rate of COVID-19 patients depressed at 6 months and with anxiety at 12 months was higher compared to controls (4.1% vs 2.7%, P=0.014 and 4.5% vs 1.1%, P=0.088, respectively). Factors significantly associated with IBS diagnosis were anamnestic allergies (OR 10.024, 95% CI 1.766-56.891, P=0.009), chronic intake of proton pump inhibitors (OR 4.816, 95% CI 1.447-16.025, P=0.010) and dyspnea (OR 4.157, 95% CI 1.336-12.934, P=0.014). Conclusion(s): Hospitalized COVID-19 patients complain less constipation and hard stools than control at 12 months after acute infection. COVID-19 patients are also more likely to develop IBS.

USING MOBILE PHONES FOR COLLECTING HEALTH INFORMATION IN THE SUB SAHARAN AFRICA DURING THE COVID-19 PANDEMIC: TAKING LESSONS FROM THE WORLD DEVELOPMENT INDICATORS DATABASE

Objective The primary aim of this study was to portray the level of spread and the dynamic of diffusion of mobile phone technology in sub-Saharan Africa during the last two decades. The secondary aim was to investigate factors related to the use of mobile phone technology in sub-Saharan Africa and to derive profiles of the most suitable areas to conduct mobile phone technology-based research. Methods The present work was based on the data collected by the World Bank database;a collection of public access data derived from yearly surveys conducted at country level. Two methods were applied to perform the selection of variables related to the diffusion of mobile phones in sub-Saharan Africa. Firstly, a Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied. Afterwards, a system of simultaneous equation was applied to estimate the model coefficients and determine the joint statistical significance. Results The number of mobile phones subscriptions in relation to the population of sub-Saharan Africa has increased consistently during the period 2000 to 2010. The rate of mobile phones subscriptions in relation to the population ranged between less than 1% to more than 90%. Urban areas and having a lower number of people leaving in slums seems to be the most suitable places to conduct mobile phone-based interviews. This information is useful in identifying countries and macro areas to conduct mobile phone interviews;and this could be extended to smallest area within a country. Discussion More effort is required to better understand how to identify areas suitable for conducting research using mobile phones and other electronic-based tools. Such an effort should be based on individual level surveys to understand not only the material possibility but also the will to participate to research based on data capturing made by mobile phones and similar tools.

IBD and COVID-19 in Italy: Comparisons between first and second pandemic wave

Background: Coronavirus disease 2019 (COVID-19), had two pandemic waves in 2020, respectively in April and November. In the general population, the first wave has been characterized by a higher prevalence in Northern Italy and a higher mortality rate compared to the second one. The aim of this study was to compare the characteristics of IBD patients and negative outcomes of COVID-19 (pneumonia, hospitalization, ventilatory support, death) between the two pandemic waves in Italy. Methods: Prospective observational cohort study. Patients with diagnosis of IBD and confirmed SARS-CoV-2 infection were enrolled. Differences between first and second wave were tested for significance using the Student's t test and Fisher's test, as appropriate. A two-tailed p value <0.05 was indicative of statistical significance. Results: We enrolled 937 IBD patients from 47 participating IBD centres across Italy (219 in the first wave, 718 in the second wave). There were no significant differences between the first and the second wave in terms of age (46.3 ± 16.0 vs. 44.1 ± 15.5 years, p=0.06) and gender (female 45.7% vs. 48.2%, p= 0.54). In the first wave, a lower percentage of patients was affected by Crohn's disease (CD): 92 (42.0%) vs. 399 (55.6%) (p<0.001) while no differences were observed for disease clinical activity: 97/219 (44.3%) vs. 280/718 (38.9%) in the first and second wave, respectively (p=0.18). Regarding biologic therapy, the percentage of patients on biologics in the two waves was similar: 119/219 (54.3%) vs. 393/718 (54.7%) (p=0.94), without differences in anti-TNFalpha, anti-integrins and anti-IL12/23 distribution. During the first wave, a significantly higher percentage of patients were from Northern Italy compared to Central-Southern Italy: 171/219 (78.1%) vs. 387/718 (53.9%), respectively (p<0.001). Overall, COVID-19 negative outcomes were significantly higher in the first wave compared to the second one: 110 (50.2%) vs. 95 (13.2%), respectively (p<0.001). Also the single negative outcomes were significantly higher in the first wave: 61/219 (27.8%) vs. 84/718 (11.7%) had pneumonia, 62/219 (28.3%) vs. 76/718 (10.6%) required hospitalization, 26/219 (11.9%) vs. 39/718 (5.4%) required ventilatory support, and 12/219 (5.5%) vs. 13/718 (1.8%) died (Figure 1). Conclusion: IBD patients had higher number of COVID-19 negative outcomes in the first wave than in second wave. In the first wave, a significantly higher percentage of patients were from Northern Italy, but no significant differences in negative outcomes were observed in comparison with those from Central- Southern Italy. Overall, findings in IBD population are coherent with those observed in the general population. (Table Presented).