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Vito Annese

Publications and source records attributed to Vito Annese.

At least 19 recordsLinked to original sources
PubMed2025

Cardiovascular Complications Are Increased in Inflammatory Bowel Disease: A Path Toward Achievement of a Personalized Risk Estimation.

Background/Objectives: The global burden of inflammatory bowel diseases (IBDs) continues to rise, with up to 50% of patients experiencing extraintestinal manifestations. Cardiovascular diseases (CVDs) are of particular concern, ranking as the second leading cause of mortality in this population. Despite a comparatively lower prevalence of traditional cardiovascular (CV) risk factors, the persistent inflammatory milieu and immune dysregulation inherent to IBD may contribute to heightened CVD risk. In this study, following a review of the current literature, an ongoing prospective trial designed to clarify CV risk profiles in IBD patients is detailed. Methods: A cohort of patients with IBD is being enrolled for comprehensive baseline evaluation of CV risk factors, lifestyle metrics, and disease characteristics. The incidence of major adverse cardiovascular events (MACEs) will be tracked and contrasted with a gender- and age-matched non-IBD cohort over a 2-year follow-up period. In cases of MACE occurrence, a multi-omics analysis-including genomic, proteomic, transcriptomic, and microbiome profiling-will be performed, along with a parallel evaluation in matched IBD controls without MACE. An artificial intelligence (AI) framework will support the analysis of this complex dataset. Results: To date, over 150 patients with IBD have been enrolled, and detailed phenotypic data and biological samples have been collected. Conclusions: We aim to introduce an IBD-specific correction factor for existing CV risk scores upon study completion. This is particularly relevant for individuals under 40 years of age, who are often inadequately assessed by current risk stratification models.

Crohn’s disease↗
PubMed2007

Continuous infusion versus bolus administration of steroids in severe attacks of ulcerative colitis: a randomized, double-blind trial.

BACKGROUND: In patients with severe attacks of ulcerative colitis (UC), IV steroids represent the first-line treatment, leading to clinical improvement in approximately 50-60% of patients. AIM: The aim of this study was to prospectively compare the efficacy and safety of different modalities of steroid administration, and to evaluate predictors of failure to therapy. MATERIALS AND METHODS: In a single-center, double-blind trial, consecutive patients with a severe attack of UC received 1 mg/kg/day of 6-methyl-prednisolone administered randomly by either a bolus injection (group A) or continuous infusion (group B). RESULTS: Sixty-six patients were enrolled (35 men, mean age 38 +/- 15, range 18-75 yr), 15 of them at their first attack of UC; in the remaining cases, the mean duration of disease was 4.5 +/- 5 yr. At inclusion, forty patients (60%) had pancolitis and the remainder had left-sided colitis. Overall, thirty-three patients (50%) underwent clinical remission after 7 days of treatment: 16 of 32 in group A and 17 of 34 in group B. Thirty-one patients eventually underwent total colectomy (12 in group A and 9 in group B), which was carried out by the first month in 10 patients (5 in each group). Twenty-eight patients (15 in group A and 13 in group B) experienced steroid-related adverse reactions. All differences between groups were not statistically significant. Previous use of steroids (OR 13.6, CI 2-86) and active smoking (OR 11.6, CI 1.4-107) were independent predictors of nonresponse. CONCLUSIONS: In severe attacks of UC, methyl-prednisolone given as a continuous infusion was no better than bolus administration in terms of efficacy and safety.

Adolescent↗
PubMed2006

Non-surgical treatment of esophageal achalasia.

Esophageal achalasia is an infrequent motility disorder characterized by a progressive stasis and dilation of the oesophagus; with subsequent risk of aspiration, weight loss, and malnutrition. Although the treatment of achalasia has been traditionally based on a surgical approach, especially with the introduction of laparoscopic techniques, there is still some space for a medical approach. The present article reviews the non-surgical therapeutic options for achalasia.

Botulinum Toxins↗
PubMed2006

Genetic variation in myosin IXB is associated with ulcerative colitis.

BACKGROUND & AIMS: Common germline genetic variation in the 3' region of myosin IXB (MYO9B) has been associated recently with susceptibility to celiac disease, with a hypothesis that MYO9B variants might influence intestinal permeability. These findings suggested the current study investigating a possible further role for MYO9B variation in inflammatory bowel disease. METHODS: Eight single-nucleotide polymorphisms (SNPs) were selected to tag common haplotypes from the 35-kb 3' region of MYO9B. These included the strongest celiac disease-associated variants reported in a Dutch cohort. These SNPs were studied in 3 independently collected and genotyped case-control cohorts of European descent (UK, Dutch, and Canadian/Italian), comprising in total 2717 inflammatory bowel disease patients (1197 with Crohn's disease, 1520 with ulcerative colitis) and 4440 controls. RESULTS: Common variation in MYO9B was associated with susceptibility to inflammatory bowel disease in all 3 cohorts examined (most associated SNP, rs1545620; meta-analysis P = 1.9 x 10(-6); odds ratio, 1.2), with the same alleles showing association as reported for celiac disease. CONCLUSIONS: MYO9B genetic variants predispose to inflammatory bowel disease. Interestingly, rs1545620 is a nonsynonymous variant leading to an amino acid change (Ala1011Ser) in the third calmodulin binding IQ domain of MYO9B. Unlike previous variants (in other genes) reported to predispose to inflammatory bowel disease, the association at MYO9B was considerably stronger with ulcerative colitis, although weaker association with Crohn's disease also was observed. These data imply shared causal mechanisms underlying intestinal inflammatory diseases.

Adolescent↗
PubMed2006

Evidence of transmission ratio distortion of DLG5 R30Q variant in general and implication of an association with Crohn disease in men.

Recently, we described the association of genetic variation in the discs large homolog 5 (DLG5) gene with inflammatory bowel disease (IBD) in a large European study sample (Stoll et al. in Nat Genet 36:476-480, 2004). Here, we report that the R30Q variant constitutes a susceptibility factor for Crohn disease (CD) in men [odds ratio (OR)=2.49, 95% confidence interval (CI) 1.53-4.06, P<0.001] but not women (OR=1.01, 95% CI=0.70-1.45, P=0.979) using multivariate logistic regression analyses in a unified study sample from Germany, Italy and Quebec. R30Q is a significant predictor for CD in men even when accounting for CARD15 and IBD5 risk variants (adjusted OR=2.41, 95% CI=1.41-4.12, P=0.001). The observed association is driven by a gender-dependent transmission ratio distortion (TRD) among healthy controls (frequency of Q allele: men 5.2%, women 11.3%), an effect that is offset in CD patients (frequency of Q allele: men 10.1%, women 10.9%). This finding is further substantiated by two non-IBD study samples, one of which consists of a newborn screening sample (newborn males 7.1%; newborn females 11%, P=0.036). Further investigation of the observed TRD may contribute towards enlightening the role of DLG5 in physiological processes influencing transmission of chromosomes to the surviving offspring, which, in turn, may help in understanding its implication in the development of CD among men.

Adult↗
PubMed2006

Direct or indirect association in a complex disease: the role of SLC22A4 and SLC22A5 functional variants in Crohn disease.

A common haplotype spanning 250 kb on chromosome 5q31 is strongly associated with Crohn disease (CD). Recently, two functional variants within the SLC22A4 and SLC22A5 genes at this locus (IBD5), L503F (c.1507C > T) and G-207C (c.-207G > C), have been proposed to contribute directly to susceptibility to CD. However, extensive linkage disequilibrium at the IBD5 locus has complicated efforts to distinguish causal variants from association of the general risk haplotype. We genotyped the SLC22A4 and SLC22A5 variants and other polymorphisms across the risk haplotype in four populations of European origin, and applied regression-based haplotype analysis to over 1,200 fully genotyped case-control pairs, modeling case/control status on the presence of one or more SNPs to test for conditional association and to identify risk haplotypes. We found highly significant association of SNPs at the IBD5 locus with Crohn disease in all populations tested. However, the frequencies of L503F and G-207C in individuals who did not carry the general IBD5 risk haplotype were not significantly different in cases and controls, with associated disease odds ratios (ORs) of 0.90 (95% CI, 0.57-1.40) and 0.90 (95% CI, 0.65-1.23), respectively. Haplotype analysis showed that addition of the SLC22A4 and SLC22A5 variants to a null model that included the background risk haplotype did not significantly improve the model fit. In addition to the common risk haplotype, several rare haplotypes had an increased frequency in cases compared to controls. This study suggests that the molecular basis for Crohn disease susceptibility at the IBD5 locus remains to be defined, and highlights the challenge of the identification of causal variants in a complex disease in regions of extensive linkage disequilibrium.

Case-Control Studies↗
PubMed2006

Haplotype-based association analysis of 56 functional candidate genes in the IBD6 locus on chromosome 19.

Evidence from four independent linkage studies and two meta-analyses of genome-wide data support the existence of a locus conferring susceptibility to inflammatory bowel diseases (IBD) in chromosomal region 19p. Identification of a susceptibility allele in this approximately 28.5 Mb region with over 600 genes is a formidable task. To tackle this problem, we undertook two approaches: (1) haplotype-based candidate-gene screen, and (2) evaluation of previously reported associations. For the former, we selected genes with potential implication in IBD pathogenesis based on published functional and expression data, typed SNPs, constructed haplotypes, screened for association in 180 IBD trios, and followed up preliminary associations in 343 IBD patients and 207 control individuals. Overall, we analyzed 465 SNPs, and 260 haplotypes distributed across 56 candidate genes. We found suggestive evidence of association (nominal P<0.01) with four genes (C3, FCER2, IL12RB1, and CRLF1) in a screening stage, but were unable to confirm these preliminary observations at follow-up. In the second approach, we typed four nonsynonymous polymorphisms in genes C3 (R102G and L314P) and ICAM1 (G241R and K469E) in four independent cohorts totaling 2178 IBD cases. We evaluated these data together with previously published reports for three of these variants (C3-Gly102, ICAM1-Arg241, and ICAM1-Glu469), in a meta-analysis. Our pooled meta-analysis provides compelling evidence against association of these variants with disease. Overall, we performed the most comprehensive candidate-gene association study for IBD to date. The information hereby generated constitutes a valuable resource to investigate other common genetic immune diseases, such as celiac disease.

Alleles↗
PubMed2006

Contribution of IBD5 locus to clinical features of IBD patients.

AIM: The aim of this study was to investigate the influence of the IBD5 locus on clinical features of inflammatory bowel disease (IBD) patients, and its possible interaction with the CARD15 gene. PATIENTS AND METHODS: A cohort of 1,199 IBD patients (570 with CD and 629 with ulcerative colitis [UC]), and 357 healthy subjects were investigated. Information on clinical features was fully available for 855 IBD patients. Two SNPs in the IBD5 locus (IGR2198a_1 and IGR2096a_1) and the three major variants of CARD15 gene were genotyped in patients and controls. RESULTS: Homozygous carriers of risk alleles were significantly more frequent in CD (22.6% for IGR2198a_1, OR = 1.6, p = 0.015; 21.9% for IGR2096a_1, OR = 1.6, p = 0.012) compared to controls (16.8% and 15.7%, respectively). The homozygote frequency was also increased in UC patients, but not significantly. No significant gene-gene interaction was detected between IBD5 and CARD15. A univariate analysis detected association between IBD5 and steno/fistulizing behavior in CD patients (OR = 1.9; p = 0.004), and presence of more extensive colitis in UC patients (OR = 1.7; p = 0.01). Results from multiple logistic regression, after correction for covariates, showed that the influence of IBD5 on clinical outcome of CD was completely masked by that of CARD15, while the influence on more extensive colitis in UC patients was confirmed. CONCLUSIONS: Our study shows that presence of the IBD5 risk alleles, particularly in the homozygous state, is associated with IBD and especially with CD, without a significant epistasis with CARD15. The contribution of CARD15 risk alleles to CD clinical features is prominent on that of IBD5.

Adolescent↗
PubMed2005

Association of DLG5 R30Q variant with inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system known as the inflammatory bowel diseases (IBD). Recently, Stoll and colleagues reported a novel finding of genetic variation in the DLG5 gene that is associated with IBD (CD and UC combined). We present here a study of the genetic variation described in that report in two well-powered, independent case-control cohorts and one family-based collection, and confirm the proposed association between IBD and the R30Q variant of DLG5 in two of the three studies. We are, however, unable to replicate the other proposed association to the common haplotype described in Stoll et al and suggest that this other finding could conceivably have been partially a statistical fluctuation and partially a result of LD with the replicated R30Q association. This study provides support for the hypothesis that DLG5 constitutes a true IBD risk factor of modest effect.

Case-Control Studies↗
PubMed2005

The IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interaction.

BACKGROUND AND AIMS: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant. One gene associated with CD has been identified: NOD2/CARD15. Two independent genome-wide scans found significant evidence (logarithm of odds [LOD] 3.6) and suggestive evidence (LOD 2.8) for linkage on locus 14q11-12, also known as the IBD4 locus. To further characterize this locus, we assessed gene-environment interaction (IBD4 x smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs as part of an ongoing international collaborative effort. PATIENTS AND METHODS: A total of 733 IBD families, comprising 892 affected sibling pairs, were genotyped for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus. Information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location was available. RESULTS: A significant distortion in the mean allele sharing (MAS) between affected siblings was observed for CD patients only at each of the four markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively). Maximum linkage for CD was observed at marker D14S261 (multipoint nonparametric linkage score 2.36; P </= 0.01; MAS 54.6%). MAS was higher in CD families in which all siblings or at least one sibling smoked compared with nonsmoking CD families (MAS, 58.90%, 57.50%, and 52.80%, respectively). CONCLUSIONS: The IBD International Genetics Consortium replicated the IBD4 locus on chromosome 14q for CD and also showed evidence for a gene-environment interaction at this locus. Further studies are needed to explore the mechanism by which smoking influences IBD4.

Adolescent↗
PubMed2005

Topical treatment of distal active ulcerative colitis with beclomethasone dipropionate or mesalamine: a single-blind randomized controlled trial.

GOALS: Therapy for active ulcerative colitis (UC) usually involves rectal formulations of corticosteroids (CS), which are characterized by the risk of systemic steroid-related adverse effects. BACKGROUND: To compare the efficacy and safety of the topically acting CS beclomethasone dipropionate (BDP) versus mesalamine (5-ASA) in the treatment of active UC. STUDY: Patients with mild to moderate distal active UC were randomized to a 6-week treatment with BDP 3 mg enema o.d. or 5-ASA 1 g enema daily in a single-blind, multicenter, parallel-group, controlled study. The primary efficacy variable was the decrease in Disease Activity Index (DAI) score. Safety variables were adrenal function, monitoring of adverse events, vital signs, and laboratory parameters. RESULTS: A total of 217 patients were enrolled and treated with BDP (n = 111) or 5-ASA (n = 106). A significant decrease in the DAI score (P < 0.05) was observed in both treatment groups, with a clinical remission rate of 36.7% in the BDP group and of 29.2% in the 5-ASA group. Both treatments were well tolerated. No changes from baseline in morning cortisol levels were observed in the BDP group. CONCLUSIONS: BDP administered as a rectal enema over a 6-week treatment period was efficacious and safe in patients with active UC, without interference with pituitary adrenal axis.

Administration, Topical↗
PubMed2005

Variants of CARD15 are associated with an aggressive clinical course of Crohn's disease--an IG-IBD study.

BACKGROUND: Three major variants of the CARD15 gene confer susceptibility to Crohn's disease (CD). Whether or not these variants correlate with specific clinical features of the disease is under evaluation. AIM: We investigated the possible association of CARD15 variants with specific clinical characteristics, including the occurrence of anti-Saccharomyces cerevisiae antibodies (ASCA) and antineutrophil cytoplasmic antibodies (ANCA), in a large cohort of inflammatory bowel disease (IBD) patients and their unaffected relatives. METHODS: Three hundred and sixteen CD patients (156 with positive family history), 408 ulcerative colitis (UC) patients (206 with positive family history), 588 unaffected relatives, and 205 unrelated healthy controls (HC) were studied. Single nucleotide polymorphisms (SNPs) R702W, G908R, and L1007finsC of the CARD15 gene were investigated and correlated to age at diagnosis, gender, family history, localization, extraintestinal manifestations, previous resective surgery, stenosing/fistulizing pattern, ANCA, and ASCA. RESULTS: Compared to HC, the frequencies of all three variants in CD were significantly increased: 8.7% versus 4.1% for R702W (p < 0.006), 7.3% versus 2.7% for G908R (p < 0.002), 9.3% versus 0.7% for L1007finsC (p < 0.00001). At least one risk allele was found in 38.2% (p < 0.0001, compared to HC), 13.7% (NS), and 15.1% of CD, UC, and HC, respectively. The L1007finsC risk allele was also significantly increased in unaffected relatives of familial (9.5%; p < 0.00001), and sporadic CD (9%; p < 0.00001), compared to HC (0.7%). Sixteen healthy relatives, carriers of two risk alleles, were asymptomatic after 5-8 yr of follow-up. CD carriers of at least one variant were younger (p= 0.03), more likely to have ileal localization (p= 0.0001), stenosing pattern (p= 0.01), previous resective surgery (p= 0.0001), and presence of ASCA (p= 0.0001). No difference in SNPs frequency between familial and sporadic cases of CD was found. CONCLUSION: In our population, both familial and sporadic CD patients carrying at least one major variant of CARD15 had an aggressive clinical course.

Adult↗
PubMed2005

Is perianal Crohn's disease associated with intestinal fistulization?

BACKGROUND: When cases of Crohn's disease (CD) are described as "fistulizing," distinctions are often not drawn between perianal and intestinal fistulization. The question, therefore, remains open as to whether or not there is truly an association between perianal fistulization and intraabdominal intestinal fistulization in CD. AIMS: We have sought to determine the association between perianal and intestinal fistulization by analyzing the cases of CD recorded in databases from six international centers. PATIENTS: Six databases provided information on 5491 cases of CD in the United States, France, Italy, and The Netherlands. Of these cases, 1686 had isolated ileal disease and 1655 had Crohn's colitis. METHODS: An association between perianal disease and internal fistulae was sought by calculating relative risks for the chance of internal fistulae among patients with perianal fistulae relative to those without. Statistical significance was calculated by the Mantel-Haenszel procedure, stratifying on the separate centers. All statistical tests and estimates were implemented using SAS for the PC. RESULTS: Among the 1686 cases with isolated ileal disease, the evidence of an association between perianal disease and internal fistulization was not consistent across centers, with relative risks ranging from 0.8 to 2.2. For patients with Crohn's colitis (n = 1655), the association was much stronger and more consistent, with an estimated common relative risk of 3.4, 95% confidence interval (2.6-4.6, p < 0.0001). CONCLUSIONS: We have found a statistically significant association between perianal CD and intestinal fistulization, much stronger and more consistent in cases of Crohn's colitis than in cases limited to the small bowel.

Anus Diseases↗
PubMed2005

Erythrocytes-mediated delivery of dexamethasone in steroid-dependent IBD patients-a pilot uncontrolled study.

BACKGROUND AND AIM: Autologous erythrocytes can be used as carriers of drugs, owing to the ability of their membrane to be opened and resealed under appropriate conditions. In this pilot uncontrolled study, we investigated efficacy and safety of dexamethasone-encapsulated erythrocytes in steroid-dependent IBD patients. MATERIALS AND METHODS: Ten patients (5 with ulcerative colitis and 5 with Crohn's disease) with steroid dependency ranging from 8 to 60 months were studied. Seven of them were in clinical remission, and the remaining three had mild activity. Eight patients were also under azathioprine or 6-MP for at least 6 months (range 6-24 months), while another two patients were intolerant to both drugs. Fifty milliliters of blood were drawn from each subject; dexamethasone 21-Phosphate (Dex 21-P) was encapsulated into erythrocytes by means of specially designed equipment, and drug-loaded erythrocytes were infused into original donors. The procedure was repeated after 4 and 8 wk, and patients were instructed to withdraw corticosteroids. RESULTS: A mean dose of 5.5+/-2.4 mg Dex 21-P was loaded in the erythrocytes at each treatment. Following re-infusion of loaded erythrocytes, plasma Dexamethasone (Dex) concentrations were detected after as long as 28 days. Steroids were completely withdrawn by the second month. After the third infusion, all patients, including the three with mild active disease, were in clinical remission. ESR levels dropped from 47+/-27 at baseline to 27+/-16 mm/h (p<0.02), and CRP levels from 1.6+/-1.3 to 0.6+/-0.5 mg/dl (p<0.02). After a mean follow-up of 12+/-3 months, six patients relapsed, and the remaining four patients remained in remission. Pre-existing steroid-related adverse effects disappeared during the follow-up. CONCLUSIONS: Loading of Dex 21-P in autologous erythrocytes is feasible and safe. The very low dose of Dex released in blood stream was able to maintain patients in clinical remission and allowed steroids withdrawal.

Adult↗
PubMed2004

Randomized controlled trial of botulinum toxin versus laparoscopic heller myotomy for esophageal achalasia.

OBJECTIVE: To compare laparoscopic cardia myotomy and fundoplication with botulinum toxin (BoTx) injection in patients with esophageal achalasia. SUMMARY BACKGROUND DATA: Although myotomy is thought to offer better results, recent studies have reported 80% success rates after 2 BoTx injections a month apart. No randomized controlled trials comparing the 2 treatments have been published so far. MATERIALS AND METHODS: Newly diagnosed achalasia patients were randomly assigned to BoTx injection or laparoscopic myotomy. Symptoms were scored; lower esophageal sphincter resting and nadir pressures were measured by manometry; barium swallow was used to assess esophageal diameter pre- and post-treatment. Eight to one hundred units of BoTx were injected twice, a month apart, at the esophagogastric junction. Myotomy included anterior partial (Dor) or Nissen fundoplication. RESULTS: Eighty patients were involved in the study: 40 received BoTx and 40 underwent myotomy. Mortality was nil. One surgical patient bled from the trocar site. Median hospital stay was 6 days for surgery; BoTox patients were treated as day-hospital admissions. All patients completed the follow-up. After 6 months, the results in the 2 groups were comparable, although symptom scores improved more in surgical patients (82% confidence interval [CI] 76-89 vs. 66% CI 57-75, P < 0.05). The drop in lower esophageal sphincter pressure was similar in the 2 groups; the reduction in esophageal diameter was greater after surgery (19% CI 13-26 vs. 5% CI 2-11, P < 0.05). Later on, symptoms recurred in 65% of the BoTx-treated patients and the probability of being symptom-free at 2 years was 87.5% after surgery and 34% after BoTx (P < 0.05). CONCLUSION: Laparoscopic myotomy is as safe as BoTx treatment and is a 1-shot treatment that cures achalasia in most patients. BoTx should be reserved for patients who are unfit for surgery or as a bridge to more effective therapies, such as surgery or endoscopic dilation.

Adolescent↗