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1.
Diagnostics (Basel) ; 14(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-39001251

RESUMO

We aimed to determine the diagnostic yield and outcome of patients receiving antithrombotic drug therapy subjected to small bowel capsule endoscopy (SBCE) for the investigation of small bowel bleeding (SBB). A multicenter retrospective analysis of collected data from all patients undergoing SBCE for the investigation of SBB from March 2003 to June 2023 was performed. The diagnostic yield of SBCE was defined as the detection of positive findings that could explain the cause of the patient's bleeding. Rebleeding was defined as evidence of bleeding within 1 year after the index episode. During the study period, 8401 patients underwent SBCE for SBB investigation. Bleeding lesions were detected in 1103/2535 (43.5%) antithrombotic users, compared to 1113/5866 (18.9%) in nonusers (p < 0.00001). Following capsule endoscopy, a therapeutic intervention was possible in 390/2216 (17.5%) patients with a bleeding lesion. Rebleeding occurred in 927 (36.5%) of antithrombotic users (36.5%), compared to 795 (13.5%) of nonusers (13.5%, p < 0.00001). Both the diagnostic yield of SBCE and the rebleeding rates were higher in patients with SBB receiving antithrombotics. Therapeutic intervention was possible in a real-world setting only for a minority of patients with positive findings.

2.
Eur J Clin Invest ; : e14283, 2024 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979834

RESUMO

BACKGROUND AND AIMS: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. METHODS: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse-switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. RESULTS: Two hundred and thirty-one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) = .002), 6 (FDR <1 × 10-10) or 12 months (FDR = .08). Clinical disease activity at baseline (only in UC) (FDR = .07) and previous exposure to biologics (FDR = .001) were risk factors for composite endpoint at 6 and 12 months. CONCLUSION: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes.

3.
Int J Mol Sci ; 25(10)2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38791570

RESUMO

INTRODUCTION: Optimizing treatment with biological agents is an ideal goal for patients with ulcerative colitis (UC). Recent data suggest that mucosal inflammation patterns and serum cytokine profiles differ between patients who respond and those who do not. Ustekinumab, a monoclonal antibody targeting the p40 subunit of interleukin (IL)-12 and IL-23, has shown promise, but predicting treatment response remains a challenge. We aimed to identify prognostic markers of response to ustekinumab in patients with active UC, utilizing information from their mucosal transcriptome. METHODS: We performed a prospective observational study of 36 UC patients initiating treatment with ustekinumab. Colonic mucosal biopsies were obtained before treatment initiation for a gene expression analysis using a microarray panel of 84 inflammatory genes. A differential gene expression analysis (DGEA), correlation analysis, and network centrality analysis on co-expression networks were performed to identify potential biomarkers. Additionally, machine learning (ML) models were employed to predict treatment response based on gene expression data. RESULTS: Seven genes, including BCL6, CXCL5, and FASLG, were significantly upregulated, while IL23A and IL23R were downregulated in non-responders compared to responders. The co-expression analysis revealed distinct patterns between responders and non-responders, with key genes like BCL6 and CRP highlighted in responders and CCL11 and CCL22 in non-responders. The ML algorithms demonstrated a high predictive power, emphasizing the significance of the IL23R, IL23A, and BCL6 genes. CONCLUSIONS: Our study identifies potential biomarkers associated with ustekinumab response in UC patients, shedding light on its underlying mechanisms and variability in treatment outcomes. Integrating transcriptomic approaches, including gene expression analyses and ML, offers valuable insights for personalized treatment strategies and highlights avenues for further research to enhance therapeutic outcomes for patients with UC.


Assuntos
Colite Ulcerativa , Biologia Computacional , Ustekinumab , Humanos , Ustekinumab/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Masculino , Feminino , Biologia Computacional/métodos , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Estudos Prospectivos , Transcriptoma , Perfilação da Expressão Gênica/métodos , Subunidade p19 da Interleucina-23/genética , Subunidade p19 da Interleucina-23/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos dos fármacos , Aprendizado de Máquina , Prognóstico
4.
United European Gastroenterol J ; 12(5): 543-551, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38419274

RESUMO

BACKGROUND: Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third-line therapies in UC patients in whom anti-TNF and vedolizumab had failed. METHODS: This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC-related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C-reactive protein, endoscopic remission, treatment withdrawal, and adverse events. RESULTS: One-hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1-q3, 5.5-18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow-up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 [95% CI: 1.06-3.50] p = 0.030). Twenty-eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow-up period (log-rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11). CONCLUSIONS: Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head-to-head clinical trials are needed as to confirm these data.


Assuntos
Colite Ulcerativa , Progressão da Doença , Piperidinas , Pirimidinas , Ustekinumab , Humanos , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Ustekinumab/uso terapêutico , Ustekinumab/efeitos adversos , Colite Ulcerativa/tratamento farmacológico , Masculino , Feminino , Pirimidinas/uso terapêutico , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Resultado do Tratamento , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Pirróis/administração & dosagem , Indução de Remissão/métodos
5.
Eur J Gastroenterol Hepatol ; 36(3): 313-317, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38179872

RESUMO

BACKGROUND: Total proctocolectomy (TPC) followed by ileal pouch-anal anastomosis (IPAA) remains the only viable option whenever different treatment modalities fail in patients with ulcerative colitis (UC). OBJECTIVE: Prospective cohort pre/post study examining the anal defecatory function and competence in UC patients undergoing TPC plus IPAA using high-resolution anorectal manometry (HR-ARM). PATIENTS: Patients undergoing TPC and IPAA were enrolled in the study and subjected to HR-ARM prior to and 6 months after surgery. The anal resting, squeeze and push pressures were recorded, together with the rectal sensation and the rectal balloon expulsion test. The number of bowel movements, symptoms/signs related to fecal incontinence, as well as the IBDQ-32 quality of life questionnaires were documented during both HR-ARM visits. RESULTS: A total of 20 consecutive UC patients were recruited in our study. The mean (SD) number of bowel movements before the TPC plus IPAA was 10.1 (2.8), while the same number after the pouch surgery was 7.7 (3.1) [ P  = 0.01]. Symptoms or signs of fecal incontinence were noted in one of our patients prior to the operation; however, none of our patients reported any such symptoms after the pouch surgery. The median (IQR) IBDQ-32 questionnaire scores before and after surgery were 121.5 (13.5) and 142.5 (16.0) respectively. At the same time, the anorectal function remained intact since both the anal resting and squeeze pressures were not significantly changed. CONCLUSION: UC patients subjected to TPC-IPAA exhibit improved bowel movements and a normal anal defecatory function and competence post-surgery.


Assuntos
Colite Ulcerativa , Bolsas Cólicas , Incontinência Fecal , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/cirurgia , Estudos Prospectivos , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Qualidade de Vida , Anastomose Cirúrgica , Bolsas Cólicas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
6.
Clin Gastroenterol Hepatol ; 22(2): 347-356.e6, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37302449

RESUMO

BACKGROUND & AIMS: We evaluated the efficacy of herbal combination of curcumin-QingDai (CurQD) in active ulcerative colitis (UC). METHODS: Part I was an open-label trial of CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index score of 5 or higher and a Mayo endoscopic subscore of 2 or higher. Part II was a placebo-controlled trial conducted in Israel and Greece, randomizing active UC patients at a 2:1 ratio to enteric-coated CurQD 3 g/d or placebo for 8 weeks. The co-primary outcome was clinical response (reduction in the Simple Clinical Colitis Activity Index of ≥3 points) and an objective response (Mayo endoscopic subscore improvement of ≥1 or a 50% fecal calprotectin reduction). Responding patients continued either maintenance curcumin or placebo alone for an additional 8 weeks. Aryl-hydrocarbon receptor activation was assessed by cytochrome P450 1A1 (CYP1A1) mucosal expression. RESULTS: In part I, 7 of 10 patients responded and 3 of 10 achieved clinical remission. Of 42 patients in part II, the week 8 co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (P = .033). Clinical response was observed in 85.7% vs 30.7% (P < .001), clinical remission in 14 of 28 (50%) vs 1 of 13 (8%; P = .01), a 50% calprotectin reduction in 46.4% vs 15.4% (P = .08), and endoscopic improvement in 75% vs 20% (P = .036) in the CurQD and placebo groups, respectively. Adverse events were comparable between groups. By week 16, curcumin-maintained clinical response, clinical remission, and clinical biomarker response rates were 93%, 80%, and 40%, respectively. CurQD uniquely up-regulated mucosal CYP1A1 expression, which was not observed among patients receiving placebo, mesalamine, or biologics. CONCLUSIONS: In this placebo-controlled trial, CurQD was effective for inducing response and remission in active UC patients. The aryl-hydrocarbon receptor pathway may merit further study as a potential UC treatment target. CLINICALTRIALS: gov ID: NCT03720002.


Assuntos
Colite Ulcerativa , Colite , Curcumina , Humanos , Colite Ulcerativa/tratamento farmacológico , Curcumina/uso terapêutico , Citocromo P-450 CYP1A1/uso terapêutico , Colite/tratamento farmacológico , Complexo Antígeno L1 Leucocitário , Indução de Remissão , Resultado do Tratamento , Método Duplo-Cego
7.
J Crohns Colitis ; 17(1): 37-48, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35767639

RESUMO

BACKGROUND AND AIMS: There are concerns regarding the potential impact of the COVID-19 outbreak on patients with inflammatory bowel disease [IBD]. We report on the impact of the COVID-19 outbreak in a European prospective cohort study of patients with IBD. PATIENTS AND METHODS: We prospectively collected data from 5457 patients with IBD nested in the ongoing I-CARE project and still followed up in April 2020, with monthly online monitoring of clinical activity, treatment, imaging and endoscopy. Investigators were also contacted to report incidental cases. RESULTS: In total, 233 [4.3%] reported COVID-19 and 12 [0.2%] severe COVID-19, with no COVID-19 deaths. The risk of COVID-19 in patients with IBD was not increased compared to the general population (standardized incidence ratio [SIR]: 1.18, 95% confidence interval [CI] [1.03-1.34], p = 0.009), as well as the risk of severe COVID-19 (SIR: 0.69, 95% CI [0.35-1.20], p = 0.93). We did not observe any negative impact of the different IBD-related medication on the risk of either COVID-19 or severe COVID-19. In 2020, the COVID-19 outbreak resulted in a drastic decrease in endoscopic and imaging procedures from March to May 2020 compared to 2018 and 2019. No impacts on clinical IBD disease activity as well as ongoing treatment were noted. CONCLUSION: No increases in either COVID-19 or severe COVID-19 incidences were observed in patients with IBD. There was no impact of COVID-19 on IBD-related medication and clinical activity. Access to endoscopy and imaging was restricted during the first months of the first COVID-19 outbreak.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Humanos , Estudos Prospectivos , Estudos de Coortes , COVID-19/epidemiologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico
8.
Ann Gastroenterol ; 35(3): 267-274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35599924

RESUMO

Background: Using data from the ulcerative colitis (UC) narrative Greece survey, part of a global survey of patients and physicians, we aimed to identify the impact of UC on patients' lives and to compare patients' and gastroenterologists' responses to questions relating to communication during the management of UC in our country. Methods: The survey was conducted online by The Harris Poll, and included 95 patients and 51 gastroenterologists. Eligible were adult UC patients who had seen a gastroenterologist in the past 12 months and had at some time taken a prescription medication (excluding those who had only ever taken 5-aminosalicylates). Patients with mild UC were capped at 20% of total survey respondents to focus the survey on patients with moderate-to-severe disease. Results: The mean time between first experienced symptoms and diagnosis of UC was 0.89 years. Most patients (82%) considered their UC to be in remission, while 98% felt satisfied with their communication with their treating gastroenterologist. However, the disease affected patients' daily life and employment adversely, with 78% reporting their UC to be mentally exhausting. Although nearly 7 in 10 physicians (69%) reported having taken steps to improve their communication skills, many patients (60%) wished they had more time at appointments with their physician, while 44% still felt uncomfortable talking about their sex life and personal relationships. Conclusions: Greek UC patients appear to be satisfied with their physicians and their disease management. Gaps in patient-physician communication relating to quality of life, emotional, and sexual/relationship concerns need to be addressed.

9.
Nutrients ; 14(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35276991

RESUMO

Aim: To establish whether the addition of probiotics to a globally accepted Helicobacter pylori (H. pylori)-eradication scheme may reduce the rates of side effects and increase the eradication rates. Methods. Prospective, randomized, placebo-controlled trial of patients receiving eradication therapy for H. pylori in the eight participating centers. All patients received a 10-day proton pump inhibitor containing non-bismuth quadruple therapeutic regimen for H. pylori eradication (omeprazole 20 mg, amoxycillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg all twice daily orally) and were randomized to receive either probiotics (group A) or placebo (group B). The probiotic used combined four probiotic strains, i.e., Lactobacillus Acidophilus, Lactiplantibacillus plantarum, Bifidobacterium lactis, and Saccharomyces boulardii. Results. Data were analyzed for 329 patients in group A and 335 patients in group B. Fifty six (17.0%) patients in group A and 170 (50.7%) patients in group B reported the occurrence of an H. pylori treatment-associated new symptom or the aggravation of a pre-existing symptom of any severity (p < 0.00001). H. pylori was successfully eradicated in 303 patients in group A (92.0%) and 291 patients in group B (86.8%), (p = 0.028). Conclusion: Adding probiotics to the 10-day concomitant non-bismuth quadruple H. pylori eradication regimen increases the eradication rate and decreases side effects.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Probióticos , Antibacterianos/efeitos adversos , Bismuto/farmacologia , Bismuto/uso terapêutico , Quimioterapia Combinada , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Probióticos/efeitos adversos , Estudos Prospectivos
10.
J Clin Med ; 11(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35160092

RESUMO

Since inflammatory bowel disease (IBD) patients were excluded from vaccine authorization studies, limited knowledge exists regarding perceptions and unfavorable effects of COVID-19 vaccination in this group. We aimed to investigate the real-world use and adverse events (AEs) of COVID-19 vaccines in Greek IBD patients. Fully vaccinated IBD patients followed in Greek centers were invited to participate. All patients filled out an anonymous online survey concerning the vaccination program, which included information regarding demographics, clinical characteristics, treatment, vaccination perceptions and potential AEs. Overall, 1007 IBD patients were included. Vaccine hesitancy was reported by 49%. Total AEs to vaccination were reported by 81% after dose 1 (D1) and 76% after dose 2 (D2), including isolated injection site reactions (36% and 24% respectively). Systemic AEs were more common after D2 (51%, D2 vs. 44%, D1, p < 0.0001). Very few patients reported new onset abdominal symptoms (abdominal pain 4% (D1), 6% (D2) and diarrhea 5% (D1), 7% (D2)). There were no serious AEs leading to emergency room visit or hospitalization. In multivariate analysis, AEs occurrence was positively associated with young age and female gender (p < 0.0005 for both doses), whereas inactive disease was negatively associated with AE in D1 (p = 0.044). SARS-CoV-2 vaccination in Greek IBD patients demonstrated a favorable and reassuring safety profile.

12.
Inflamm Bowel Dis ; 28(1): 87-95, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34042157

RESUMO

BACKGROUND: Improving treatment outcomes with biological therapy is a demanding current need for patients with inflammatory bowel disease. Discovery of pretreatment prognostic indicators of response may facilitate patient selection and increase long-term remission rates. We aimed to identify baseline mucosal gene expression profiles with predictive value for subsequent response to or failure of treatment with the monoclonal antibody against integrin α4ß7, vedolizumab, in patients with active ulcerative colitis (UC). METHODS: Mucosal expression of 84 immunological and inflammatory genes was quantified in RNA extracted from colonic biopsies before vedolizumab commencement and compared between patients with or without response to treatment. Significantly differentiated genes were further validated in a larger patient cohort and within available public data sets, and their functional profiles were studied accordingly. RESULTS: In the discovery cohort, we identified 21 genes with a statistically significant differential expression between 54-week responders and nonresponders to vedolizumab. Our validation study allowed us to recognize a "core" mucosal profile that was preserved in both discovery and validation cohorts and in the public database. The applied functional annotation and analysis revealed candidate dysregulated pathways in nonresponders to vedolizumab, including immune cell trafficking, TNF receptor superfamily members mediating noncanonical NF-kB pathway, in addition to interleukin signaling, MyD88 signaling, and toll-like receptors (TLRs) cascade. CONCLUSIONS: Nonresponse to vedolizumab in UC is associated with specific pretreatment gene-expression mucosal signatures and dysregulation of particular immunological and inflammatory pathways. Baseline mucosal and/or systemic molecular profiling may help in the optimal stratification of patients to receive vedolizumab for active UC.


Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Fármacos Gastrointestinais , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Transcriptoma , Resultado do Tratamento
13.
Dig Dis Sci ; 67(3): 1007-1017, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33751325

RESUMO

BACKGROUND: Optimization of treatment with biologics is currently an unmet need for patients with ulcerative colitis (UC). Real-world studies provide neutral estimates of drug efficacy and safety within unselected patient populations and allow for the recognition of specific characteristics that affect response to therapy. AIMS: We aimed to depict the efficacy of vedolizumab in patients with UC in a real-world setting and identify prognosticators of improved outcomes. METHODS: Patients with active UC who commenced treatment with vedolizumab were prospectively followed up. Patient-reported outcomes (PROs) and clinical/endoscopic-reported outcomes were recorded at baseline and at weeks 14 and 54. Predefined endpoints of early and persistent efficacy were analyzed against clinical characteristics to identify prognostic factors for response. RESULTS: We included 96 patients (anti-TNF-exposed = 38.5%). At week 14, 73 patients (76%) had clinical response and 54 (56.3%) clinical remission. At week 54, the primary endpoint of vedolizumab persistence was met by 72 patients (75%), whereas steroid-free clinical remission by 59.4%. Among patients who had endoscopy, rates for mucosal healing (Mayo endoscopic score of 0) were 29.8% at week 14 and 44.6% at week 54, respectively. Vedolizumab treatment led to significant improvements in quality of life. Corticosteroid-refractory or anti-TNF-refractory disease, articular manifestations, and high baseline UC-PRO2 were associated with decreased efficacy of vedolizumab in the primary and secondary outcomes. CONCLUSIONS: Vedolizumab is characterized by high efficacy and long-term treatment persistence in UC. More aggressive disease, as indicated by refractoriness to steroids or anti-TNFs and elevated baseline PROs, may predict suboptimal response and help pre-treatment prognostic stratification of patients.


Assuntos
Colite Ulcerativa , Anticorpos Monoclonais Humanizados , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Grécia , Humanos , Qualidade de Vida , Indução de Remissão , Estudos Retrospectivos , Esteroides/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral
14.
Eur J Gastroenterol Hepatol ; 33(1S Suppl 1): e810-e817, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34402469

RESUMO

OBJECTIVES: COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. METHODS: Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). RESULTS: We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. CONCLUSIONS: IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.


Assuntos
COVID-19 , Doenças Inflamatórias Intestinais , Adulto , Doença Crônica , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , SARS-CoV-2 , Inibidores do Fator de Necrose Tumoral
15.
World J Gastroenterol ; 27(24): 3568-3580, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34239270

RESUMO

Pancreatic cancer is one of the highest and in fact, unchanged mortality-associated tumor, with an exceptionally low survival rate due to its challenging diagnostic approach. So far, its treatment is based on a combination of approaches (such as surgical resection with or rarely without chemotherapeutic agents), but with finite limits. Thus, looking for additional space to improve pancreatic tumorigenesis therapeutic approach, research has focused on gene therapy with unexpectedly growing horizons not only for the treatment of inoperable pancreatic disease, but also for its early stages. In vivo gene delivery viral vectors, despite few disadvantages (possible immunogenicity, toxicity, mutagenicity, or high cost), could be one of the most efficient cancer gene therapeutic strategies for clinical application due to their superiority compared with other systems (ex vivo delivery strategies). Their dominance consists of simple preparation, easy operation and a wide range of functions. Adenoviruses are one of the most common used vectors, inducing strong immune as well as inflammatory reactions. Oncolytic virotherapy, using the above mentioned in vivo viral vectors, is one of the most promising non-pathogenic, highly-selective cytotoxic anti-cancer therapy using anti-cancer agents with high anti-tumor potency and strong oncolytic effect. There have been a variety of targeted therapeutic and pre-clinical strategies tested for gene therapy in pancreatic cancer such as gene-editing systems (e.g., clustered regularly interspaced palindromic repeats-Cas9), RNA interference technology (e.g., microRNAs, short hairpin RNA or small interfering RNA), adoptive immunotherapy and vaccination (e.g., chimeric antigen receptor T-cell therapy) with encouraging results.


Assuntos
Terapia Viral Oncolítica , Neoplasias Pancreáticas , Edição de Genes , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia
16.
Eur J Gastroenterol Hepatol ; 33(1S Suppl 1): e59-e65, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35048645

RESUMO

Since December 2019, the severe acute respiratory syndrome coronavirus 2 has constituted a serious threat to global health. So far, there is little published evidence on the laboratory features of coronavirus disease 2019 (COVID-19). We have reviewed laboratory findings from multiple studies, mostly relating to the digestive system, since the virus outbreak. Laboratory data from older coronaviruses endemics, as well as other RNA viruses, were also reported. Although the main route of transmission is considered to be respiratory droplets, the distribution of ACE2 receptors in the gastrointestinal tract in combination with the detection of the virus in feces may imply a potential fecal-oral transmission route, and thus, emphasis should be given to patients with gastrointestinal symptoms. Interestingly, there is evidence that severe acute respiratory syndrome coronavirus 2 displays similar laboratory and clinical findings with older members of the coronavirus family, and so, comparable diagnostic and therapeutic approaches may be used. Regarding laboratory abnormalities, lymphopenia appears to be the most common finding, together with coagulation disorders and inflammatory markers elevation, reflecting a sustained systemic response. Abnormal liver and, occasionally, pancreatic tests are also common and even more severe in patients with gastrointestinal symptoms or diseases. Thus, the aim of this study is to focus on the laboratory and pathophysiologic side of this novel disease in order to strengthen current knowledge and urge further research. Detailed investigation of numerous studies may suggest a common laboratory pattern between COVID-19 patients. It is important for clinicians not to underestimate patients with gastrointestinal comorbidities, as they have been associated with severe COVID-19 disease.


Assuntos
COVID-19 , Pandemias , Trato Gastrointestinal , Humanos , Laboratórios , Aerossóis e Gotículas Respiratórios , SARS-CoV-2
17.
Eur J Gastroenterol Hepatol ; 33(1S Suppl 1): e909-e915, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35048657

RESUMO

OBJECTIVE: To compare recurrence rates among three endoscopic treatment modalities for 5-9 mm left-sided colorectal polyps. METHODS: Consecutive adults referred for elective colonoscopy (1/2015-1/2018) with at least one polyp of eligible size (5-9 mm) located distally to the splenic flexure were randomly assigned (1:1:1) to one of three treatment modalities: (1) cold snare polypectomy (CSP), (2) hot snare polypectomy (HSP) and (3) argon plasma coagulation (APC) ablation (50-60 W, flow: 2 l/min). The polyp site was marked with an endoscopic tattoo, and a follow-up colonoscopy with scar biopsies was performed >6 months after the index procedure. Outcomes were polyp recurrence rate and occurrence of complications. RESULTS: One hundred nineteen patients were enrolled, of whom 112 (62.5% males, mean age 61.1 ± 9.9 years) with 121 polyps (CSP, 39; HSP, 45; APC, 37) returned for follow-up colonoscopy. Mean polyp size was 6.7 ± 0.91 mm, 58% were located in the sigmoid, 33% in the rectum and 8% in the descending colon. The majority of polyps resected by CSP or HSP were neoplastic (tubular adenomas: 25.9%, tubulovillous adenomas: 11.1% and sessile serrate adenomas/polyps: 17.5%). No cases of delayed bleeding or perforation occurred. Scar biopsies at follow-up colonoscopy (performed after a mean interval of 13.4 ± 3.8 months) revealed 7 (5.8%) cases of polyp recurrence, showing no significant difference among the three treatment groups [CSP, 3/39 (7.7%); HSP, 1/45 (2.2%); APC, 2/37 (5.4%); P = 0.51). CONCLUSIONS: CSP, HSP and APC-ablation are effective and well-tolerated treatment modalities for 5-9 mm left-sided colorectal polyps. The present randomized study did not detect any difference in polyp recurrence rate among the three endoscopic techniques.


Assuntos
Adenoma , Pólipos do Colo , Adenoma/patologia , Adulto , Idoso , Coagulação com Plasma de Argônio/efeitos adversos , Cicatriz/etiologia , Cicatriz/patologia , Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Eur J Gastroenterol Hepatol ; 33(3): 364-371, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32925506

RESUMO

BACKGROUND: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have been associated with improved outcomes in inflammatory bowel disease. We aimed to investigate any possible effect of antihypertensive medications on inflammatory bowel disease course. METHODS: One hundred and fifty inflammatory bowel disease patients with hypertension were compared using a 1:1 ratio with age- and gender-matched control patients with inflammatory bowel disease. The class of antihypertensive medication, traditional risk factors for atherosclerosis, inflammatory bowel disease characteristics, and history (surgery, hospitalizations, and treatment) were retrospectively analyzed. RESULTS: Of 150 (44.7% Crohn's disease) patients with hypertension, 46.7% were on angiotensin receptor blockers, 30.6% on angiotensin-converting enzyme inhibitors, 40% on ß-blockers, and 40.7% on calcium channel blockers. Univariate analysis revealed significantly higher rates of traditional risk factors for atherosclerosis among antihypertensive users. When analyzing by class of antihypertensive medication, angiotensin receptor blockers were significantly associated with milder course as indicated by less frequent immunomodulator (P = 0.039) and steroid use (P = 0.041). Rates of lifetime steroids were statistically significantly lower among angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (odds ratio = 1.191, 95% confidence interval, 1.005-1.411). After adjustment with confounding factors, only angiotensin receptor blockers were associated with milder inflammatory bowel disease course (P = 0.037) and lower rates of immunomodulator use (P = 0.038). CONCLUSIONS: Our study suggests a possible protective effect of angiotensin receptor blockers on overall inflammatory bowel disease course by targeting the renin-angiotensin system. Their effect on inflammatory bowel disease needs to be studied in larger cohorts.


Assuntos
Hipertensão , Doenças Inflamatórias Intestinais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Sistema Renina-Angiotensina , Estudos Retrospectivos
20.
World J Gastroenterol ; 26(31): 4579-4588, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32884218

RESUMO

The pandemic of coronavirus disease 2019 (COVID-19), caused by a newly identified ß-coronavirus (SARS-CoV-2) has emerged as a dire health problem, causing a massive crisis for global health. Primary method of transmission was firstly thought to be animal to human transmission. However, it has been observed that the virus is transmitted from human to human via respiratory droplets. Interestingly, SARS-CoV-2 ribonucleic acid (RNA) has been isolated from patient stools, suggesting a possible gastrointestinal (GI) involvement. Most commonly reported clinical manifestations are fever, fatigue and dry cough. Interestingly, a small percentage of patients experience GI symptoms with the most common being anorexia, diarrhea, nausea and vomiting. The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples. The exact incidence of digestive symptoms is a matter of debate. The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms' mechanism. Cases with solely GI symptoms have been reported in both adults and children. Viral RNA has also been detected in stool and blood samples, indicating the possibility of liver damage, which has been reported in COVID-19 patients. The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis, however data from these cases is lacking. The aim of this review is firstly, to briefly update what is known about the origin and the transmission of SARS-CoV-2, but mainly to focus on the manifestations of the GI tract and their pathophysiological background, so that physicians on the one hand, not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other, to have SARS-CoV-2 on their mind when the "gastroenteritis" type symptoms predominate.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Gastroenteropatias/virologia , Hepatopatias/virologia , Pneumonia Viral/fisiopatologia , Adulto , COVID-19 , Teste para COVID-19 , Criança , Técnicas de Laboratório Clínico , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/transmissão , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Saúde Global , Humanos , Hepatopatias/diagnóstico , Hepatopatias/fisiopatologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/transmissão , Fatores de Risco , SARS-CoV-2
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