Effect of Tofacitinib on One-Year Colectomy Risk in Anti-TNF Refractory Ulcerative Colitis: A Prospective Multicenter Italian Study.

BACKGROUND: Tofacitinib is an oral Janus kinase inhibitor recently approved to induce and maintain remission in ulcerative colitis (UC). AIMS: Considering the number of anti-TNF non-responders, this study aims to assess the effectiveness and safety of tofacitinib in a cohort of multi-failure patients with moderate-to-severe UC at 52 weeks. METHODS: From January 2021 to March 2023, we performed a prospective multicenter study observing adult patients with moderate-to-severe UC starting tofacitinib after an anti-TNF failure for a 52-week-long period. Effectiveness and safety were assessed in terms of colectomy rate, clinical remission and response, endoscopic remission, steroid-free clinical remission, and rate of adverse events. RESULTS: We included 58 patients with UC with an age of 42 ± 14.4 years, 59% males, 96.6% left-sided or pancolitis, who were failure to a single (65.5%) or more than one anti-TNF (34.5%). Only 6 (10.3%) patients underwent colectomy. Colectomy was clinically associated with the necessity and the number of extra cycles of tofacitinib 10 mg bid at W8 (p = 0.023) and W24 (p = 0.004), and with a higher partial Mayo score at W8 (p = 0.025). At W52, clinical remission, clinical response, and steroid-free clinical remission were 53.4%, 43.1%, and 48.3%, respectively. Of 22 performed colonoscopies at W52, 11 (50%) showed endoscopic remission. Adverse events occurred in 14 (24.1%) patients, but only 2 (3.4%) led to tofacitinib discontinuation. CONCLUSIONS: In a real-life setting of patients with anti-TNF refractory UC, tofacitinib has proved to be effective in preventing colectomy and inducing clinical and endoscopic remission at 52 weeks with a good safety profile.

Glucose variability increases during minimally invasive procedures in very preterm infants.

The objective of this study is to assess the effect of neonatal procedures on glucose variability in very preterm infants. Preterm infants (≤ 32 weeks gestation and/or birthweight ≤ 1500 g) were started on continuous glucose monitoring (CGM) on day 2 of birth and monitored for 5 days. Minimally invasive (heel stick, venipunctures) and non-invasive (nappy change, parental presence) procedures were recorded. CGM data were analyzed 30 min before and after each procedure. The primary outcome was the coefficient of glucose variation (CV = SD/mean) before and after the procedure; SD and median glucose were also evaluated. We analyzed 496 procedures in 22 neonates (GA 30.5 weeks [29-31]; birthweight 1300 g [950-1476]). Median glucose did not change before and after each procedure, while CV and SD increased after heel prick (p = 0.017 and 0.030), venipuncture (p = 0.010 and 0.030), and nappy change (p < 0.001 and < 0.001), in the absence of a difference during parental presence. CONCLUSIONS: Non-invasive and minimally invasive procedures increase glucose variability in the absence of changes of mean glucose. WHAT IS KNOWN: • Minimally invasive procedures - including nappy change - may increase neonatal stress in preterm infants. WHAT IS NEW: • Continuous glucose monitoring provides a quantitative measure of neonatal stress during neonatal care procedures demonstrating an increase of glucose variability.

The aftermath of SARS-CoV-2 in NICU: saving or checking accounts? Projected cost-effectiveness analysis.

In the aftermath of the SARS-CoV-2 pandemic, we revised the cost-effectiveness of the exploited interventions in neonatal intensive care unit, to redefine future strategies for hospital management. Costs were revised with respect to the lockdown R0 or under different R0 scenarios to estimate the cost-effectiveness of the screening program adopted. Weekly nasopharyngeal swabs for parents, neonates, and personnel were the major cost during the pandemic, although they effectively reduced the number of cases in our unit.Conclusion: Parents and healthcare personnel testing appears to be an effective strategy due to the high number of contact they have within the hospital environment and outside, able to minimize the cases within our unit. What is Known: • Costs of universal COVID-19 tests for parents, neonates, and NICU personnel have not been evaluated during the COVID-19 pandemic in neonatal intensive care unit in Europe. What is New: • Weekly nasopharyngeal swabs for parents, neonates, and personnel were the major cost during the COVID-19 pandemic in NICU. • Parents and healthcare personnel testing was effective to reduce costs related to COVID-19 due to the high number of contact they have within the hospital environment and outside.

Trends in neonatal emergency transport in the last two decades.

Although maternal antenatal transfer is the preferred option, some infants inevitably need urgent transport to a tertiary neonatal care facility after birth. This study aimed to investigate trends over time in patient characteristics and respiratory management in a large series of neonatal emergency transfers, in order to provide health caregivers an up-to-date profile of such patients and their therapeutic needs. Trends in patient characteristics and respiratory management were evaluated in 3337 transfers by the Eastern Veneto Neonatal Emergency Transport Service in 2000-2019. Joinpoint regression analysis was performed to evaluate trends and to estimate annual percentage changes (APCs). Proportions of preterm neonates increased (APC2000-2012 2.25%), then decreased (APC2012-2019 - 6.04%). Transfers at birth increased (APC2000-2013 2.69%), then decreased (APC2013-2019 - 5.76%). Proportion of neonates with cardiac and surgical diseases declined (APCs2000-2019 - 6.82% and - 3.32%), while proportion of neonates with neurologic diseases increased (APC2000-2019 8.62%). Use of nasal-continuous-positive-airway-pressure (APC2000-2019 9.72%) and high-flow-nasal-cannula (APC2007-2019 58.51%) at call, and nasal-continuous-positive-airway-pressure (APC2000-2019 13.87%) and nasal-intermittent-mandatory-ventilation (APC2000-2019 32.46%) during transfer increased. Mechanical ventilation during transfer decreased (APC2014-2019 - 10.77%). Use of oxygen concentrations at 21% increased at call and during transfer (APCs 2000-2019 2.24% and 2.44%), while oxygen concentrations above 40% decreased at call and during transfer (APCs 2000-2019 - 3.93% and - 5.12%).Conclusion: Our findings revealed a shift toward a more "gentle" approach and the reduced use of oxygen in respiratory management. Equipment and team expertise should meet the requirements of such changing patients and their therapeutic needs. What is Known: • Although antenatal transfer is the preferred option, some infants inevitably need urgent transport to a tertiary neonatal care facility after birth. • Trend studies investigating cohort information with appropriate statistical methods represent useful instruments to detect changes over time. What is New: • Our findings revealed marked changes in patient characteristics and respiratory management in a large series of neonatal emergency transfers during the last two decades. • Equipment and team expertise should meet the requirements of such changing patients and their therapeutic needs.

Response Assessed by Ultrasonography as Target of Biological Treatment for Crohn's Disease.

BACKGROUND & AIMS: Mucosal healing, determined by ileocolonoscopy, is a goal for treatment of Crohn's disease (CD), but this is an invasive assessment procedure. We investigated whether response to tumor necrosis factor (TNF) antagonists, determined by small-intestine contrast ultrasonography, associates with long-term outcomes. METHODS: We performed observational study of 80 patients with CD treated with anti-TNF agents for at least 1 year who underwent serial small intestine contrast ultrasonography (SICUS) at the University of Rome, in Italy. SICUS was used to evaluate disease site (based on bowel wall thickness), extent of lesions, and presence of complications. Inclusion criteria required pre-therapy SICUS with follow-up SICUS after 18 months. At second SICUS, patients were assigned to categories of complete or partial responder or non-responder. CD-related outcomes (corticosteroid need, hospitalization, and surgery) were assessed at 1 year from the second SICUS, using multivariate models, and were analyzed after long term follow up (5 years) using Kaplan-Meier survival analysis. RESULTS: Based on SICUS, after a median of 18 months, 36 patients (51%) were complete responders, 30 were partial responders (34%), and 13 were non-responders (15%). At 1 year from the second SICUS, no patients with a complete response, based on ultrasonography, underwent surgery, in comparison to partial responders (P = .0003) or non-responders (P = .001). Complete responders used smaller amounts of corticosteroids than partial responders (P = .0001) or non-responders (P < .0001). Complete responders required fewer hospitalizations than non-responders (P = .001). Kaplan-Meier survival analysis of long-term follow up data demonstrated a lower cumulative probability of need for surgery, hospitalization, and need for steroids among SICUS-categorized complete responders (P < .0001, P = .003 and P = .0001 respectively) than SICUS-categorized non-responders. CONCLUSIONS: In patients with CD, response to anti-TNF agents, determined by SICUS, is associated with better long-term outcomes than partial or no response. Ultrasonographic assessment therefore provides a relatively non-invasive method for monitoring response to treatment in patients with CD.

Universal screening of high-risk neonates, parents, and staff at a neonatal intensive care unit during the SARS-CoV-2 pandemic.

Since February 21, 2020, SARS-CoV-2 has spread exponentially worldwide. Neonatal patients needing intensive care are considered a vulnerable population. To report the results of a policy based on multi-timepoint surveillance for SARS-CoV-2 of all neonates admitted to the neonatal intensive care unit (NICU), their parents, and all healthcare providers in a part of Italy with a high prevalence of the infection. Observational study conducted from 21 February to 21 April 2020. Intervention consisted of (a) parental triage on arrival at the neonatal ward; (b) universal testing with nasopharyngeal swabs and blood testing for SARS-CoV-2 IgM and IgG antibodies; (c) use of continuous personal protective equipment at the NICU by parents and staff. A total of 6726 triage procedures were performed on 114 parents, and 954 nasopharyngeal swabs were collected from 226 individuals. Five (2.2%) asymptomatic individuals (2 parents and 3 healthcare providers) tested positive on nasopharyngeal swabs and were kept isolated for 14 days. Of 75 admitted newborn, no one tested positive on nasopharyngeal swabs or antibody tests. Three parents presented with fever or flu-like symptoms at triage; they tested negative on swabs.Conclusion: With universal screening of neonates, parents, and staff, there were no cases of SARS-CoV-2 infection among the neonates admitted to a NICU in an area with a high incidence of SARS-CoV-2. Our experience could be usefully compared with other strategies with a view to developing future evidence-based guidelines for managing high-risk neonates in case of new epidemics. What is Known: • The novel coronavirus named SARS-CoV-2 has since spread worldwide at a remarkable rate, with more than 2.5 million confirmed cases. • Pediatric population may be less affected from COVID-19 than adult population but infants and newborn babies seem to be more vulnerable to SARS-CoV-2 infection. What is New: • Using an approach based on triage; testing with nasopharyngeal swabs and serology; and use of personal protective equipment, there were no cases of SARS-CoV-2 infection among neonates in a NICU in a high incidence of SARS-CoV-2 area. • Positive and asymptomatic individuals were identified and isolated early allowing the containment of infection's spread among healthcare providers and parents.

HandS ECMO: Preliminary Experience With "Hub and Spoke" Model in Neonates With Meconium Aspiration Syndrome.

We aim to evaluate clinical outcomes of emergent extracorporeal membrane oxygenation (ECMO) implantation in newborns with life-threatening meconium aspiration syndrome (MAS) in peripheral hospitals with Hub and Spoke (HandS) setting. We retrospectively reviewed all neonates presenting with MAS, with no other comorbidities, treated with HandS ECMO, in peripheral hospitals. Team activation time (TAT) was described as the time from first alerting call to ECMO support initiation. From May 2014 to December 2016, 4 patients met our inclusion criteria. In addition, 2 cases occurred on the same day, requiring a second simultaneous HandS ECMO team activation. All patients were younger than 8 days of life (1, 1, 4, and 7), with a mean BSA 0.21 ± 0.03m2 , and TAT of 203, 265, 320, and 340 min. One patient presented ventricular fibrillation after priming administration. Veno-arterial ECMO was established in all patients after uneventful surgical neck vessels cannulation (right carotid artery and jugular vein). Mean time from skin incision to ECMO initiation was 19 ± 1.4 min. Mean length of ECMO support was 2.75 ± 1.3 days. All patients were weaned off support without complications. At a mean follow up of 20.5 ± 7.8 months, all patients are alive, with no medications, normal somatic growth, and neuropsychological development. MAS is a life-threatening condition that can be successfully managed with ECMO support. A highly trained multidisciplinary HandS ECMO team is crucial for the successful management of these severely ill newborns in peripheral hospitals.

Protocols for early discharging of premature infants: an empirical assessment on safety and savings.

Background Preterm newborns may be discharged when clinical conditions are stable. Several criteria for early discharge have been proposed in the literature. This study carried out the first quantitative comparison of their impact in terms of hospitalization savings, safety and costs. Methods This study was based on the clinical histories of 213 premature infants born in the Neonatal Intensive Care Unit of Padova University Hospital between 2013 and 2014. Seventeen early discharge criteria were drawn from the literature and retrospectively applied to these data, and computation of hospitalization savings, safety and costs implied by each criterion was carried out. Results Among the criteria considered, average gains ranged from 1.1 to 10.3 hospital days and between 0.3 and 1.1 fewer infections per discharged infant. Criteria that led to saving more hospital days had higher cost-effectiveness in terms of crisis and infection, and they spared infants from more infections. However, episodes of apnea and bradycardia were detected after the potential early discharge date for all criteria, with a mean number of episodes numbering between 0.3 and 1.4. Conclusion The results highlight a clear trade-off between days saved and health risks for infants, with potential consequences for health care costs.

Heated, Humidified High-Flow Nasal Cannulae as a Form of Noninvasive Respiratory Support for Preterm Infants and Children with Acute Respiratory Failure.

Heated, humidified high-flow delivered by nasal cannulae (HHHFNC) is increasingly used for noninvasive respiratory support in preterm infants and critically ill children due to its perceived effectiveness and ease of use. Evidence from randomized controlled trials suggests that HHHFNC and continuous positive airway pressure (CPAP) are equally effective as postextubation support in preterm infants. HHHFNC is also used for weaning preterm infants from CPAP. Data on HHHFNC used as the primary support for treating respiratory distress syndrome are conflicting. HHHFNC use in preterm infants is associated with reduced nasal trauma. Inability to measure the pressure generated by HHHFNC systems is a concern because overexpansion can lead to an air leak and lung injury. Great caution is warranted when HHHFNC is used in extremely low-birth-weight infants (who were rarely included in these randomized controlled trials) because a recent retrospective study found its use is associated with a higher likelihood of bronchopulmonary dysplasia or death in this population. HHHFNC has also become popular in pediatric intensive care units and pediatric wards as a method for delivering oxygen and noninvasive respiratory support. Most published studies were conducted on infants and young children with bronchiolitis. The results of a few observational studies and two randomized trials suggest that HHHFNC therapy is effective in the treatment of bronchiolitis. This review discusses the proposed mechanisms of action behind HHHFNC, the results of observational studies, and the evidence emerging from clinical trials on the use of HHHFNC in preterm infants and children critically ill with bronchiolitis.

Bromodomain-containing 4 is a positive regulator of the inflammatory cytokine response in the gut.

BACKGROUND AND AIM: Bromodomain-containing protein 4 (BRD4), one of the components of the bromodomain and extraterminal domain (BET) family, is a transcriptional and epigenetic regulator of cellular proliferation and cytokine production. In this study, we assessed whether BRD4 regulates the cytokine response in inflammatory bowel diseases (IBD). MATERIALS AND METHODS: BRD4 expression was analyzed in intestinal mucosal samples of patients with ulcerative colitis (UC), patients with Crohn's disease (CD), normal controls (CTRs), and mice with chemically-induced colitis by real-time PCR, Western blotting, and confocal microscopy. Cytokine production was evaluated in lamina propria mononuclear cells (LPMCs) of IBD patients and mucosal tissues of colitic mice treated with BRD4 inhibitors. Finally, we evaluated the effect of JQ1, an inhibitor of the BRD4 signaling pathway, on the course of murine colitis. RESULTS: BRD4 RNA and protein expression was up-regulated in the inflamed mucosa of patients with UC and patients with CD as compared to the uninvolved areas of the same patients and CTRs, and in the inflamed colon of colitic mice. Knockdown of BRD4 with a specific antisense oligonucleotide in IBD LPMCs led to reduced expression of TNF-α, IL-6, IFN-γ, and IL-17A. Administration of JQ1 to colitic mice inhibited the inflammatory cytokine response and attenuated the ongoing colitis. CONCLUSIONS: This is the first study showing the up-regulation of BRD4 in IBD and suggesting the role of such a protein in the positive control of the inflammatory cytokine response in the gut.

Accuracy of small-intestine contrast ultrasonography, compared with computed tomography enteroclysis, in characterizing lesions in patients with Crohn's disease.

BACKGROUND & AIMS: Small-intestine contrast ultrasonography (SICUS) is a radiation-free technique that can detect intestinal damage in patients with Crohn's disease (CD). We evaluated the diagnostic accuracy of SICUS in determining the site, extent, and complications of CD, compared with computed tomography (CT) enteroclysis as the standard. METHODS: We performed a retrospective analysis of data from 59 patients with CD evaluated by SICUS and CT enteroclysis 3 months apart, between January 2007 and April 2012. We evaluated disease site (based on bowel wall thickness), extent of lesions, and presence of complications (stenosis, prestenotic dilation, abscess, or fistulas) using CT enteroclysis as the standard. Sensitivity, specificity, and diagnostic accuracy were calculated. We determined the correlations in maximum wall thickness and disease extent in the small bowel between results from SICUS and CT enteroclysis. RESULTS: SICUS identified the site of small bowel CD with 98% sensitivity, 67% specificity, and 95% diagnostic accuracy; it identified the site of colon CD with 83% sensitivity, 97.5% specificity, and 93% diagnostic accuracy. Results from SICUS and CT enteroclysis correlated in determination of bowel wall thickness (rho, 0.79) and disease extent (rho, 0.89; P < .0001 for both). SICUS detected ileal stenosis with 95.5% sensitivity, 80% specificity, and 91.5% diagnostic accuracy, and prestenotic dilation with 87% sensitivity, 67% specificity, and 75% diagnostic accuracy. SICUS detected abscesses with 78% sensitivity, 100% specificity, and 97% diagnostic accuracy, and fistulas with 78.5% sensitivity, 95.5% specificity, and 91.5% diagnostic accuracy. CONCLUSIONS: SICUS identified lesions and complications in patients with CD with high levels of sensitivity, specificity, and accuracy compared with CT enteroclysis. SICUS might be used as an imaging tool as part of a focused diagnostic examination of patients with CD.

Echopattern parameter as an aid to profile Crohn's disease patients.

BACKGROUND: Intestinal ultrasonography (US) allows for the characterization of the intestinal lesions and provides information on transmural inflammation. The aim of the study was to assess the clinical relevance of echopattern and correlation with Crohn's disease (CD) behavior and activity. METHODS: We performed a prospective study including CD patients assessed by intestinal US. The echopattern was classified as hypoechoic, hyperechoic and stratified. Color-doppler US was also performed in the thickest segment. RESULTS: One hundred CD patients were enrolled. The hypoechoic echopattern was significantly correlated with penetrating behavior (r = 0.44, p<0.0001), active disease (r = 0.21, p = 0.034), C-reactive protein/Fecal Calprotectin (r = 0.31, p = 0.004; r = 0.34, p = 0.031, respectively) and steroids (r = 0.33, p = 0.0008). Hypoechoic echopattern was associated with younger age than stratified (p = 0.046) and hyperechoic (p = 0.018) echopatterns. Bowel wall thickness was greater in the hypoechoic group than in the hyperechoic/stratified groups (p = 0.011 and p<0.0001, respectively). Hypoechoic echopattern was associated with fistulas (r = 0.52, p<0.0001) and increased vascularization (r = 0.32, p = 0.001). The hyperechoic echopattern showed a significant correlation with stricturing disease and an inverse correlation with fistulas. During a follow up period of 6 months, patients with hypoechoic echopattern had an increased risk of biological therapy need or surgery. CONCLUSIONS: The characterization of bowel wall echopattern allows for the identification of different CD behaviors.

Niclosamide Enema for Active Distal Ulcerative Colitis: A Phase 1, Open-Label Study.

BACKGROUND: Oral and rectal formulations of 5-aminosalicylic acid are the first-line therapy for mild-to-moderate, distal ulcerative colitis (UC), but such a treatment is not effective in one-third of patients. Niclosamide is a small molecule, developed and approved as an orally administered drug to treat helminthic infections, with an excellent safety profile. Preclinical work showed that niclosamide is an anti-inflammatory agent, thereby providing the rationale to explore its safety and efficacy in patients with UC. This phase 1, open-label trial was aimed at assessing the safety of niclosamide formulated as an enema in patients with mild-to-moderate, distal UC, who relapsed on maintenance therapy with oral and/or rectal 5-aminosalicylic acid. METHODS: Seventeen patients with active UC received niclosamide enema (150 mg/60 mL) twice a day for 6 weeks. The primary endpoint was the safety of niclosamide treatment. Secondary endpoints included clinical remission and improvements in endoscopic Mayo/histologic scores. Endoscopic remission percentages exclude participants meeting criteria at baseline for endoscopic remission. RESULTS: Niclosamide was well tolerated by all 17 patients that were enrolled and treated. No serious adverse event was registered. Fifteen mild adverse events were registered in 6 patients and considered to be unrelated to the treatment. Clinical remission was achieved in 10 (59%) of 17 patients. Improvements of endoscopic Mayo score and histologic Geboes score were seen in 7 (58%) of 12 and 7 (41.2%) of 17 patients, respectively. CONCLUSIONS: Niclosamide enema treatment is safe and well tolerated. Niclosamide improves clinical symptoms and endoscopic/histologic signs of UC; however, appropriately designed placebo-controlled clinical trials are required to confirm efficacy.

Severe acute respiratory syndrome coronavirus 2 infection does not worsen the course of inflammatory bowel disease in the long term.

BACKGROUND: The long-term outcome of inflammatory bowel disease (IBD) patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is under investigation. AIM: To assess, in a prospective study, whether a recent SARS-CoV-2 infection increases the risk of IBD relapse within 12 months. METHODS: From March to April 2021, all IBD patients with recent (<2 months) SARS-CoV-2 infection (Cases) were enrolled. For each enrolled Case, four IBD Controls with no history of infection were considered. Clinical course of IBD was recorded for 12 months. Inclusion criteria: well defined diagnosis of IBD; age ≥18 and ≤85 years; 12-month follow-up; consent. Exclusion criteria: incomplete data; SARS-CoV-2 infection after enrollment. Additional inclusion criteria: recent SARS-CoV-2 infection for Cases; no history of SARS-CoV-2 infection for Controls. Data expressed as median [range]. Statistical analysis: Student-t-Test, Mann-Whitney U-test, χ2 test, multivariate logistic regression model [odds ratio (95% confidence interval)], Kaplan-Meier curves. RESULTS: One hundred forty-three IBD patients were enrolled. The analysis included 118 patients (22 met the exclusion criteria, three lost at follow-up): 29 (24.6%) Cases and 89 (75.4%) Controls. Demographic and clinical characteristics were comparable between groups. During the 12-month study, the frequency of IBD relapse was comparable between Cases and Controls [8 (27%) vs 19 (21%); P = 0.65]. At univariate analysis, SARS-CoV-2 infection was not a risk factor for IBD relapse within 12 months [1.5 (0.6-3.9); P = 0.34]. At multivariate analysis, IBD activity at baseline was the only risk factor for relapse [3.2 (1.1-9.1); P = 0.03]. Kaplan-Meier curves showed that survival from IBD relapse was comparable between Cases and Controls (P = 0.33). CONCLUSION: In a prospective 12-month study, a recent SARS-CoV-2 infection did not increase the risk of clinical relapse of IBD in the long term.

Hidradenitis suppurativa and inflammatory bowel disease in a nested case-control study.

BACKGROUND: Association between Hidradenitis Suppurativa (HS) and Inflammatory Bowel Disease (IBD) has been suggested. AIMS: To assess characteristics of HS and IBD in patients with or without concomitant IBD. METHODS: In a prospective, nested case-control study, each IBD patient with concomitant HS (Case) was retrospectively matched with 4 patients with HS and no IBD (Controls) for gender and age (±5 years).HS was classified according to the Hurley score and the International Hidradenitis Suppurativa Severity Score System (IHS4). Data were expressed as mean (Standard Deviation). Statistical analysis included Student-t Test or Mann-Whitney Test, χ2 test, univariate and multivariate logistic regression. RESULTS: The study population included 125 patients with HS: 25 with IBD, 100 matched Controls with no IBD. IBD group included 19 (76%) Crohn's disease and 6 (24%) Ulcerative Colitis patients. Obesity, familial HS and perianal HS were less frequent in Cases than in Controls (1[4%] vs 25(25%];p = 0.02; 1[4%] vs 21(21%];p = 0.04; 1[4%] vs 31(31%];p = 0.005, respectively).HS was less severe in Cases when assessed by the IHS4 (5.9 ± 4 vs 9 ± 6.7;p = 0.04).Complete drug-induced response for HS was more frequent in IBD (13[53%] vs28 (28%]; p = 0.04). CONCLUSION: Clinical characteristics of HS and of patients differed between Cases and Controls. Present findings suggest the need to appropriately search and assess skin lesions compatible with HS in IBD.

Mucinous and Signet-Ring Cell Colonic Adenocarcinoma in Inflammatory Bowel Disease: A Case-Control Study.

A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum.

Frequency and Predictors of Dysplasia in Pseudopolyp-like Colorectal Lesions in Patients with Long-Standing Inflammatory Bowel Disease.

Current endoscopic surveillance programs do not consider inflammatory bowel disease (IBD)-associated post-inflammatory polyps (pseudopolyps) per se clinically relevant, even though their presence seems to increase the risk of colorectal cancer (CRC). However, it remains unclear whether the link between pseudopolyps and CRC is indirect or whether some subsets of pseudopolyp-like lesions might eventually undergo neoplastic transformation. This study aimed to assess the frequency and predictors of dysplasia in pseudopolyp-like lesions in a population with long-standing colonic IBD. This was a retrospective, single-center study including patients with a colonic IBD (median disease duration of 192 months) and at least a pseudopolyp-like lesion biopsied or resected in the period from April 2021 to November 2022. One hundred and five pseudopolyps were identified in 105 patients (80 with ulcerative colitis and 25 with Crohn's disease). Twenty-three out of 105 pseudopolyp samples (22%) had dysplastic foci, and half of the dysplastic lesions were hyperplastic. Multivariate analysis showed that the age of the patients (odds ratio (OR) 1.1; p = 0.0012), size (OR 1.39; p = 0.0005), and right colonic location (OR 5.32; p = 0.04) were independent predictors of dysplasia, while previous exposure to immunosuppressors/biologics and left colonic location of the lesions were inversely correlated to dysplasia (OR 0.11; p = 0.005, and OR 0.09; p = 0.0008, respectively). No differences were seen between ulcerative colitis and Crohn's disease patients. Lesions with a size greater than 5 mm had a sensitivity of 87% and a specificity of 63% to be dysplastic. These data show that one-fourth of pseudopolyp-like lesions evident during surveillance colonoscopy in patients with longstanding IBD bear dysplastic foci and suggest treating such lesions properly.

Endoscopic Predictors of Neoplastic Lesions in Inflammatory Bowel Diseases Patients Undergoing Chromoendoscopy.

Dye-based chromoendoscopy (DCE) with targeted biopsies is recommended for surveillance of patients with long-standing inflammatory bowel diseases (IBD), but endoscopic features that predict dysplasia are not fully clarified. We here aimed at identifying predictive factors of dysplastic/neoplastic lesions in IBD patients undergoing DCE. Two-hundred-and-nineteen patients were consecutively and prospectively enrolled from October 2019 to March 2022. One-hundred-and-forty-five out of 219 patients underwent DCE, and 148 lesions were detected in 79/145 (54%) patients. Thirty-nine lesions (26%) were dysplastic and one of them contained a CRC. Among these lesions, 7 (17.9%) had Kudo pit pattern I-II and 32 (82.1%) had a neoplastic pit pattern (Kudo III-IV). Multivariate analysis showed that neoplastic lesions Kudo III-IV (OR: 5.8, 95% CI: 2.3−14.6; p = 0.0002), lesion's size (OR 1.16, 95% CI: 1.06−1.26; p = 0.0009), and polypoid lesions according to Paris Classification (OR 7.4, 95% CI: 2.7−20.2; p = 0.0001) were independent predictors of dysplasia. A cut-off of lesion's size > 7 mm was identified as the best predictor of dysplasia. Among such features, Kudo pit pattern III-IV had the highest sensitivity and specificity to predict dysplasia (79% and 80%, respectively). Lesions with all three endoscopic features had a sensitivity of 90% and specificity of 100% to predict dysplasia. In contrast, non-polypoid lesions were inversely associated with dysplasia (OR 0.13, 95% CI: 0.05−0.36; p = 0.0001). These findings indicate that, in IBD patients, DCE-evidenced polypoid lesions with Kudo pit pattern III-IV and size > 7 mm are frequently dysplastic.

GATA6 Deficiency Leads to Epithelial Barrier Dysfunction and Enhances Susceptibility to Gut Inflammation.

BACKGROUND AND AIMS: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases [IBD], but the mechanisms that lead to such a defect are not fully understood. This study was aimed at characterising the factors involved in the defective barrier function in IBD. METHODS: Transcriptome analysis was performed on colon samples taken from healthy controls [CTR] and IBD patients. Expression of GATA-binding factor 6 [GATA6], a transcription factor involved in intestinal epithelial cell differentiation, was evaluated in colon samples taken from CTR and IBD patients by real-time polymerase chain reaction [PCR] and immunohistochemistry. Intestinal sections of wild-type and Gata6del mice, which exhibit a conditional Gata6 deletion in intestinal epithelial cells and which are either left untreated or receive subcutaneous indomethacin or rectal trinitrobenzene sulphonic acid, were stained with haematoxylin and eosin. In parallel, some Gata6del mice received antibiotics to deplete intestinal flora. Mucosal inflammatory cell infiltration and cytokine production were evaluated by flow cytometry and real-time PCR, respectively, and tight junction proteins were examined by immunofluorescence. Intestinal barrier integrity was assessed by fluorescein isothiocyanate [FITC]-dextran assay. RESULTS: Multiple genes involved in cell commitment/proliferation and wound healing were differentially expressed in IBD compared with CTR. Among these, GATA6 was significantly decreased in the IBD epithelium compared with CTR. In mice, conditional deletion of GATA6 in the intestinal epithelium induced primarily epithelial damage, diminished zonula occludens-1 expression, and enhanced intestinal permeability, ultimately resulting in bacteria-driven local immune response and enhanced susceptibility to gut inflammation. CONCLUSIONS: Reduced expression of GATA6 promotes intestinal barrier dysfunction, thus amplifying intestinal inflammatory pathology.

Successful Control of an Outbreak by Phenotypically Identified Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae in a Neonatal Intensive Care Unit.

BACKGROUND: Premature newborns represent a vulnerable population, at high risk of acquiring nosocomial infections during neonatal intensive care unit (NICU) admission. Multidrug-resistant organisms represent the greatest concern due to their intrinsic virulence and the limited therapeutic options. Resistant Enterobacterales are a growing threat for critically ill neonates, with increasing numbers of NICU outbreaks caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales being described. This study reports the early detection and successful control of an outbreak caused by ESBL-producing Klebsiella pneumoniae (ESBL-KP) in an Italian NICU in February 2021. RESULTS: A total of 13 newborns tested positive for ESBL-KP between 2-9 February 2021, of whom four (31%) had a bloodstream infection. Two were critically ill, extremely premature newborns who died because of multiple comorbidities, and two were cured after treatment with meropenem. All other patients survived and were either discharged home or moved to other hospitals/wards in good clinical condition. ESBL-KP ST45 was found in all isolates by multilocus sequence typing (MLST) analysis. An outbreak control plan was set, including surveillance cultures for all neonates, NICU environments, and medical devices, along with the extended use of contact precautions and cohorting. In addition, the infection control plan was carried out through reinforcement and enhancement measures to guarantee maximal compliance. The outbreak was successfully controlled in seven days, given that no further cases were identified after 9 February. The source of the ESBL-KP outbreak was not identified through environmental sampling. CONCLUSIONS: Thanks to multidisciplinary management, a threatening outbreak of ESBL-KP in a NICU was controlled in few days. The prompt recognition of the event onset and the adoption of infection control interventions helped contain the bacteria spread on the ward.