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Background: This study aimed to assess the distribution of esophageal inflammation in patients with eosinophilic esophagitis (EoE) and its impact on diagnosis and outcome., Aims and Methods: Data from consecutive adult EoE patients who were followed-up at four Italian referral centers from October 2022 to October 2023 were retrospectively collected., Results: One hundred forty-nine patients were included. Proximal EoE was observed in 8.1 % of patients; distal EoE in 27.5 %; and diffuse EoE in 64.4 %. Allergic rhinitis was more prevalent in distal and diffuse than proximal EoE (72.5 % vs. 61.5 % vs 33.3 %; P = 0.049). The prevalence of asthma, atopic dermatitis, oral allergy syndrome, and gastroesophageal reflux disease was not significantly different among the three EoE extent groups. Endoscopic inflammatory features at diagnosis were more prevalent in proximal EoE (91.7 % vs. 53.8 % distal [P = 0.01] vs. 66 % diffuse[P = 0.05]). No significant differences in fibrotic features and esophageal stenoses were observed. The clinical and histological remission rates after first-line therapy were comparable in all groups., Conclusion: Esophageal inflammation in EoE more frequently involves the entire esophagus, followed by isolated distal and proximal involvement. No clear correlation was observed between the histological extent of EoE at diagnosis and comorbidities or treatment response., Competing Interests: Declaration of competing interest Edoardo Vincenzo Savarino has served as speaker for Abbvie, Abivax, Agave, AGPharma, Alfasigma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Galapagos, Johnson&Johnson, JB Pharmaceuticals, Innovamedica/Adacyte, Eli Lilly, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Dr. Falk, Eli Lilly, Fenix Pharma, Johnson&Johnson, JB Pharmaceuticals, Merck & Co, Nestlè, Pfizer, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Takeda, Unifarco; he received research support from Bonollo, Difass, Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici; Nicola de Bortoli has served as speaker for: Reckitt-Benkiser, Malesci, Sofar, Dr Falk. Advisory Board: Astra-Zenecahe; the other authors have no disclosures to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD)., Aims: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD., Methods: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted., Results: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay., Conclusion: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background. The survival benefit of complete versus infarct-related artery (IRA)-only revascularization during the index hospitalization in patients resuscitated from an out-of-hospital cardiac arrest (OHCA) with multivessel disease is unknown. Methods. We considered all the OHCA patients prospectively enrolled in the Lombardia Cardiac Arrest Registry (Lombardia CARe) from 1 January 2015 to 1 May 2021 who underwent coronary angiography (CAG) at the Fondazione IRCCS Policlinico San Matteo (Pavia). Patients’ prehospital, angiographical and survival data were reviewed. Results. Out of 239 patients, 119 had a multivessel coronary disease: 69% received IRA-only revascularization, and 31% received a complete revascularization: 8 during the first procedure and 29 in a staged-procedure after a median time of 5 days [IQR 2.5−10.3]. The complete revascularization group showed significantly higher one-year survival with good neurological outcome than the IRA-only group (83.3% vs. 30.4%, p < 0.001). After correcting for cardiac arrest duration, shockable presenting rhythm, peak of Troponin-I, creatinine on admission and the need for circulatory support, complete revascularization was independently associated with the probability of death and poor neurological outcome [HR 0.3 (95%CI 0.1−0.8), p = 0.02]. Conclusions. This observation study shows that complete myocardial revascularization during the index hospitalization improves one-year survival with good neurological outcome in patients resuscitated from an OHCA with multivessel coronary disease.

(1) Background: Villous atrophy is an indication for small bowel capsule endoscopy (SBCE). However, SBCE findings are not described uniformly and atrophic features are sometimes not recognized; (2) Methods: The Delphi technique was employed to reach agreement among a panel of SBCE experts. The nomenclature and definitions of SBCE lesions suggesting the presence of atrophy were decided in a core group of 10 experts. Four images of each lesion were chosen from a large SBCE database and agreement on the correspondence between the picture and the definition was evaluated using the Delphi method in a broadened group of 36 experts. All images corresponded to histologically proven mucosal atrophy; (3) Results: Four types of atrophic lesions were identified: mosaicism, scalloping, folds reduction, and granular mucosa. The core group succeeded in reaching agreement on the nomenclature and the descriptions of these items. Consensus in matching the agreed definitions for the proposed set of images was met for mosaicism (88.9% in the first round), scalloping (97.2% in the first round), and folds reduction (94.4% in the first round), but granular mucosa failed to achieve consensus (75.0% in the third round); (4) Conclusions: Consensus among SBCE experts on atrophic lesions was met for the first time. Mosaicism, scalloping, and folds reduction are the most reliable signs, while the description of granular mucosa remains uncertain.

Data regarding double switching from originator infliximab (IFX) to IFX biosimilars in inflammatory bowel diseases (IBDs) are lacking. The purpose of this study was to evaluate the safety and efficacy of switching from originator IFX to CT-P13 and subsequently to SB2 (double switch) in patients with IBD. Patients undergoing IFX-double switch in eight Centers in Lombardy (Italy) from November 2018 to May 2019 were retrospectively analyzed. The IFX discontinuation rate, incidence and type of adverse events (AEs), and clinical remission rate were recorded. A comparison with a control group of patients with IBD single-switched from originator IFX to CT-P13 was performed, before and after an inverse probability of treatment weighting (IPTW)-based propensity score analysis. Fifty-two double-switched patients with IBD were enrolled. The 24- and 52-week proportions of patients continuing on IFX therapy following the second switch (CTP13 → SB2) were 98% (95% confidence interval [CI] 94%-100%) and 90% (95% CI 81%-99%), respectively. Four patients experienced a total of five AEs, all graded 1-3 according to Common Terminology Criteria for Adverse Events (CTCAE). No infusion reactions were observed. The 24-week and follow-up end clinical remission rates following the second switch were 94% and 88%, respectively. No differences were observed in the safety and efficacy outcomes by comparing the double-switch group with a single-switch group of 66 patients with IBD; all these results were confirmed by IPTW-adjusted analysis. The study suggests both the safety and efficacy of the double switch from originator IFX to CT-P13 and SB2 in patients with IBD is maintained. This strategy may be associated with potential cost implications., (© 2021 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aim: To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI., Methods: This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days. Pharmacodynamic analyses were performed at five time points: baseline, and 1, 2, 4 and 12 h after the loading dose, and measured as ASA reaction units (ARU) by the Verify Now System. An ARU more than 550 was considered as nonresponsiveness to study drugs. The primary end point was the different rate of patients with ARU more than 550 at 2 h after the loading dose of oral vs. intravenous ASA. Secondary end points included the comparison of ARU more than 550 at the other time points and the comparison of continuous ARU at each time point., Results: The study was planned with a sample size of 68 patients, but it was prematurely stopped due to slow enrollment after the inclusion of 23 patients, 12 randomized to oral ASA and 11 to intravenous lysine acetylsalicylate. At 2 h the rate of patients with ARU more than 550 was numerically but not significantly higher in patients receiving oral ASA as compared with intravenous lysine acetylsalicylate (33 vs. 14.2%; Δ -0.19, 95% confidence interval -0.59-0.21, P = 0.58). The difference over time was NS (P = 0.98), though the prevalence of ARU more than 550 was higher at the other time points. Both routes of administration reduced ARU values over time, though with no overall significant difference between profiles (P overall = 0.48)., Conclusion: In patients with STEMI undergoing pPCI the rate of nonresponsiveness to ASA was not different comparing an oral 'noncoated' loading dose of ASA with an intravenous bolus injection of lysine acetylsalicylate. However, as patient enrollment was prematurely terminated, this study is underpowered to draw a definite conclusion., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.

Competing Interests: The authors declare that they have no conflict of interest.

Background: Provisional T-stenting (PS) is generally recommended to treat patients with coronary bifurcation disease (CBD) percutaneously, but PS may not fit all complex bifurcation anatomies. Therefore, several types of up-front 2-stent techniques have been described. We aimed to identify the best percutaneous coronary intervention (PCI) technique to manage patients with CBD., Methods: We systematically reviewed randomized controlled trials (RCTs) including patients undergoing CBD PCI which included several types of PCI techniques-PS, double-kissing (DK) crush, T-stenting and protrusion, culotte, dedicated bifurcation stents, crushing, and T-stenting-and we compared device-oriented clinical events (DOCEs), a composite of cardiac death, target-vessel myocardial infarction, stent thrombosis, and target-lesion or target-vessel revascularization, in a network meta-analysis. We included 26 RCTs, leading to a pooled population of 10,339 patient-years and a total of 1229 DOCEs., Results: The DK-crush technique was associated with the lowest DOCE rate, with a relative risk of 0.62 (95% CI 0.42-0.92) compared with the PS technique. DK-crush had the highest probability (model likelihood 90.2%, area under the cumulative ranking curve 98.0%) of being the best technique among those explored to reduce DOCEs in patients receiving CBD PCI., Conclusions: When a 2-stent strategy is considered in a patient with CBD, the DK-crush technique reduces DOCEs compared with other bifurcation techniques based on all available RCTs., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aims: To systematically review literature comparing bare metal stent (BMS) to drug-eluting stent (DES) in end-stage renal disease (ESRD) patients on dialysis. ESRD patients on dialysis often suffer from accelerated atherosclerosis and higher rate of stent-related complications including major adverse cardiovascular events. Because dialysis usually qualifies ineligibility for randomized clinical trials, an evidenced-based stent choice for these patients is scarce., Methods: PUBMED, CINHAL, COCHRANE, EMBASE and WEB OF SCIENCE were searched for studies comparing BMS vs. DES outcome in ESRD patients on dialysis., Results: Twenty studies including 64 232 patients were considered. The use of DES was significantly associated with a reduction in all-cause mortality [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.76-0.89], death from a cardiovascular cause (OR 0.80, 95% CI 0.76-0.84) and target lesion revascularization/target vessel revascularization (OR 0.73, 95% CI 0.53-1.00). No significant difference was found in stent thrombosis (OR 1.08, 95% CI 0.50-2.33) and myocardial infarction incidence (OR 0.91, 95% CI 0.69-1.20)., Conclusions: Our meta-analysis shows a significant reduction in all-cause and cardiovascular mortality with the use of DES over BMS in dialyzed patients. Despite the lack of randomized studies, systematic use of DES in these high-risk patients should thus reasonably be considered as a first option in percutaneous coronary intervention candidates.

Competing Interests: None

Competing Interests: None, (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims: To describe the contemporary management by cardiologists of patients after an episode of myocardial infarction (MI)., Methods: The EYESHOT Post-MI was a prospective, observational, nationwide study aimed to evaluate the management of patients referring to cardiologists 1 to 3 years from the last MI event., Results: Over a 3-month period, 1633 consecutive patients [median 22 (IQR 15-28) months from MI] were enrolled: 1028 (63.0%) at the second and 605 (37.0%) at the third year from MI. During the 12 months prior to enrolment, the majority of patients received a transthoracic echocardiogram (60% and 54%), followed by coronary angiography (24% and 16%, in the second and third year from MI groups, respectively). At the time of enrolment, the majority of patients were prescribed on statins (93%) and beta-blockers (82%), without significant differences between the 2 groups. A dual antiplatelet therapy (DAPT) was used more frequently among patients presenting during the second compared to the third year from MI (40% vs 24%; p < 0.0001). At multivariable analysis, the time interval from last MI (2 vs 3 years: OR 2.27; 95% CI 1.79-2.88; p < 0.0001) and a previous percutaneous coronary intervention with multiple stents (OR 3.46; 95% CI 2.19-5.47; p < 0.0001) resulted as the major independent predictors of DAPT persistence at the time of enrolment., Conclusions: This contemporary registry provides unique insights into the current management of post-MI patients and represents an opportunity to further improve the long-term treatment of this high-risk population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Elevated serum uric acid (eSUA) was associated with unfavorable outcome in patients with ST-segment elevation myocardial infarction (STEMI). However, the effect of eSUA on myocardial reperfusion injury and infarct size has been poorly investigated. Our aim was to correlate eSUA with infarct size, infarct size shrinkage, myocardial reperfusion grade and long-term mortality in STEMI patients undergoing primary percutaneous coronary intervention., Methods: We performed a post-hoc patients-level analysis of two randomized controlled trials, testing strategies for myocardial ischemia/reperfusion injury protection. Each patient underwent acute (3-5 days) and follow-up (4-6 months) cardiac magnetic resonance. Infarct size and infarct size shrinkage were outcomes of interest. We assessed T2-weighted edema, myocardial blush grade (MBG), corrected Thrombolysis in myocardial infarction Frame Count, ST-segment resolution and long-term all-cause mortality., Results: A total of 101 (86.1% anterior) STEMI patients were included; eSUA was found in 16 (15.8%) patients. Infarct size was larger in eSUA compared with non-eSUA patients (42.3 ± 22 vs. 29.1 ± 15 ml, P = 0.008). After adjusting for covariates, infarct size was 10.3 ml (95% confidence interval 1.2-19.3 ml, P = 0.001) larger in eSUA. Among patients with anterior myocardial infarction the difference in delayed enhancement between groups was maintained (respectively, 42.3 ± 22.4 vs. 29.9 ± 15.4 ml, P = 0.015). Infarct size shrinkage was similar between the groups. Compared with non-eSUA, eSUA patients had larger T2-weighted edema (53.8 vs. 41.2 ml, P = 0.031) and less favorable MBG (MBG < 2: 44.4 vs. 13.6%, P = 0.045). Corrected Thrombolysis in myocardial infarction Frame Count and ST-segment resolution did not significantly differ between the groups. At a median follow-up of 7.3 years, all-cause mortality was higher in the eSUA group (18.8 vs. 2.4%, P = 0.028)., Conclusion: eSUA may affect myocardial reperfusion in patients with STEMI undergoing percutaneous coronary intervention and is associated with larger infarct size and higher long-term mortality.

One of the most common causes of chronic diarrhea is ascribed to microscopic colitis (MC). MC is classified in subtypes: collagenous colitis (CC) and lymphocytic colitis (LC). Patients with MC report watery, non-bloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient's health-related quality of life. A greater awareness, and concomitantly an increasing number of diagnoses over the last years, has demonstrated that the incidence and prevalence of MC are on the rise. To date, colonoscopy with histological analysis on multiple biopsies collected along the colon represents the unique accepted procedure used to assess the diagnosis of active MC and to evaluate the response to medical therapy. Therefore, the emerging need for less-invasive procedures that are also rapid, convenient, standardized, and reproducible, has encouraged scientists to turn their attention to the identification of inflammatory markers and other molecules in blood or feces and within the colonic tissue that can confirm a MC diagnosis. This review gives an update on the biomarkers that are potentially available for the identification of inflammatory activity, related to CC and LC.