In Silico Analysis of the Aromaticity of Some Carbo-Metallabenzenes and Carbo-Dimetallabenzenes (Carbo-mers Proposed from Metallabenzenes).

In the current work, we introduce a novel class of molecules termed carbo-metallabenzenes, and their aromaticity has been comprehensively analyzed. The molecules were strategically designed with the insertion of acetylene (C≡C or C2) units in some selected metallabenzenes. Furthermore, if a second metallic unit is inserted (replacing a sp2 carbon) in the carbo-metallabenzenes rings, a new family of carbo-mers is generated, and this second group has been named as carbo-dimetallabenzenes. The primary objective of this work is to ascertain, through various methodologies, whether these newly proposed molecules retain the aromatic characteristics observed in carbo-benzene. The methodologies employed for bond analysis and aromaticity exploration include the analysis of the molecular orbitals, energy decomposition analysis, electron density of delocalized bonds, magnetically induced current density, and the induced magnetic field (Bind). This study sheds light on that the insertion of the metallic centers reduces the electronic delocalization and their aromaticity is, in some cases, comparable with the electronic delocalization of the inorganic iminobora-borazine and also provides valuable insights into their electronic structure through a multifaceted analysis.

Meta-analysis: Real-world effectiveness and safety of ustekinumab in patients with ulcerative colitis.

BACKGROUND: Evidence on real-world outcomes of ustekinumab for ulcerative colitis (UC) patients is needed. AIMS: To summarise evidence on the real-world outcomes of ustekinumab for UC and conduct a meta-analysis of effectiveness and safety data. METHODS: A systematic search was conducted through September 2022 in electronic databases for observational studies evaluating ustekinumab for UC. A random-effects meta-analysis model was used to calculate the pooled effect sizes (percentages or incidence rates [IRs]) of effectiveness and safety outcomes. RESULTS: In all, 19 studies were included with 3786 patients. More than 92% of patients were previously treated with any biologic, 61.1% with both anti-TNF and vedolizumab and 16.4% with any biologic and tofacitinib. Clinical remission was achieved in 45.4% at week 8 (95% CI: 30.1%-60.6%), 43.8% (38.4%-49.2%) at weeks 12-16, 44.6% (35.9%-53.3%) at month 6, and 50.6% (36.3%-64.8%) at month 12. Response was achieved in 61.2%, 59.4%, 65.2% and 76.8% at weeks 8, 12-16, month 6 and 12, respectively. CS-free remission was achieved in 18.7%, 36.8%, 34.5% and 39% at weeks 8, 12-16, month 6 and 12, respectively. Overall, 58.2% of patients had endoscopic improvement at month 12. Almost 30% of the patients needed dose escalation, which was effective in 40% of these patients. The IRs of colectomy, adverse events (AEs), serious AEs and serious infections were 4.8, 7.9, 0.8 and 0.3 per 100 patient-years, respectively. CONCLUSIONS: This meta-analysis confirms the effectiveness and safety of ustekinumab in a highly treatment-refractory population of UC patients.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Association of golimumab trough concentrations during maintenance with clinical, biological, endoscopic and histologic remission in patients with ulcerative colitis.

BACKGROUND: Optimal golimumab concentration thresholds for important outcomes during maintenance are lacking. AIMS: To investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multi-centre, cross-sectional study included patients with UC on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS ≤2 + faecal calprotectin <250 µg/g) (2.21 vs. 1.47, p = 0.041), endoscopic healing (Mayo endoscopic subscore 0) (2.52 vs. 1.47, p = 0.003), histologic remission (Geboes index ≤2.0) (2.33 vs. 1.50, p = 0.02) and disease clearance (clinical remission endoscopic healing + histologic remission) (2.52 vs. 1.70, p = 0.009), compared with those not meeting these criteria. Golimumab concentrations were significantly higher in patients who avoided golimumab dose escalation/discontinuation during follow-up (2.24 vs. 0.98, p = 0.012). Receiver-operating characteristic analyses identified golimumab thresholds [area under the curve] of 0.85 [0.76], 1.90 [0.76], 2.29 [0.75], 1.79 [0.68], 2.29 [0.72] and 1.56 [0.71] µg/ml as associated with clinical remission, combined remission, endoscopic healing, histologic remission, disease clearance and long-term event-free persistence with golimumab, respectively. CONCLUSIONS: Golimumab trough concentrations during maintenance are associated with favourable treatment outcomes including endoscopic healing, histologic remission and long-term persistence on golimumab. We identified the optimal golimumab thresholds most closely associated with key outcomes.

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Real-World Effectiveness and Safety of Tofacitinib in Patients With Ulcerative Colitis: Systematic Review With Meta-Analysis.

BACKGROUND: Knowledge of the real-world effectiveness and safety of tofacitinib for ulcerative colitis (UC) is relevant to confirm the benefit observed in clinical trials. METHODS: This systematic review and meta-analysis evaluated the real-world effectiveness of tofacitinib for moderate to severely active UC. The primary outcome was clinical remission evaluated at week 8, weeks 12 to 16, and month 6. Secondary outcomes were response, corticosteroid-free remission, mucosal healing, colectomy, and safety. RESULTS: Seventeen studies with a total of 1162 patients with UC were included. Remission (11 studies) was achieved in 34.7% of patients at week 8 (95% confidence interval [CI], 24.4%-45.1%), 47% at weeks 12 to 16 (95% CI, 40.3%-53.6%), and 38.3% at month 6 (95% CI, 29.2%-47.5%) at month 6 duplicated. Response was achieved in 62.1%, 64.2%, 50.8%, and 41.8% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Corticosteroid-free remission (5 studies) was achieved in 38.4%, 44.3%, 33.6%, and 31% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Mucosal healing was achieved in 48.3% and 45.3% of patients at week 8 and weeks 12 to 16, respectively. Patients who were biologic-naïve (11.6%) had a significantly higher rate of response at week 8 (1.38; 95% CI, 1.03-1.84). The incidence rates of serious adverse events and herpes zoster was 8.9 and 6.9 per 100 patient-years, respectively. CONCLUSIONS: This meta-analysis of real-world studies confirms the effectiveness of tofacitinib in a highly refractory population of patients with moderate to severely active UC. Tofacitinib showed an acceptable safety profile. These findings were consistent with clinical trials and further support the use of tofacitinib in UC.

Metallaborazines: To Be or Not To Be Delocalized.

In the current work, the analysis of the electronic delocalization of some metallacycles, based on borazine, was realized by employing magnetic criteria, such as the induced magnetic field and magnetically induced current densities, and electronic criteria, such as adaptative natural density partitioning and the analysis of molecular orbitals. The current metallaborazines were generated from isoelectronic substitutions. The main question is whether the electronic delocalization increases or decreases. The results showed that metal-N bonded borazines could be cataloged as delocalized compounds. On the other hand, the metal-B bonded borazines could be cataloged as nonaromatic (or weak aromatic) compounds based on the results of this analysis.

Correction to "In Silico Analysis of the Electronic Delocalization in Some Double Fused-Ring Metallabenzenes".

[This corrects the article DOI: 10.1021/acsomega.1c00632.].

In Silico Analysis of the Electronic Delocalization in Some Double Fused-Ring Metallabenzenes.

In the current work, some metallabenzenes with one and several fused rings were analyzed in terms of their electronic delocalization. These fused-ring metallabenzenes are known as metallabenzenoids, and their aromatic character is not free of controversy. The systems of the current work were designed from crystallographic data of some synthesized molecules, and their electronic delocalization (aromaticity) was computationally examined in terms of the molecular orbital analysis (Hückel's rule), the induced magnetic field, and ring currents. The computational evidence allows us to understand if these molecules are or are not aromatic compounds.

Reception of Dietary and Other Health-Related Lifestyle Advice to Address Non-communicable Diseases in a Primary Care Context: A Mixed-Method Study in Central Argentina.

An effective way to address risk factors for non-communicable chronic diseases (NCD) and reduce healthcare costs is by using sound health-related advice (HRA) to promote healthy lifestyle habits. In Argentina, however, few studies have examined the context in which HRA is communicated and undertaken by patients at the primary care level. In this study, we assessed the reception of HRA using a mixed-method approach in a central area of Argentina. A total of 1,044 participants from the community were contacted and sociodemographic characteristics, health-related lifestyle factors, and medical history were collected. A calendar with health messages was provided to participants and its usage was assessed after 1 year. Additionally, semi-structured interviews were conducted with 34 patients attending a local primary healthcare center. The results show that HRA was given more frequently to individuals with higher mean age, lower educational level, and to females. Participants with a chronic health condition are at a higher chance of receiving advice to reduce salt intake and maintain a healthy weight. Dietary advice is offered along with other lifestyle recommendations. The use of alcohol and tobacco is usually addressed together. HRA was primarily received in the context of an NCD diagnosis and advice was directed, especially, to risky behaviors. The HRA to increase the intake of fruits and vegetables was mentioned less frequently. Patients at the healthcare center greatly appreciated receiving an HRA, especially when given in a tailored, written, and detailed form, and acknowledged its importance to prevent or control a chronic health condition as part of the medical treatment but showed concern regarding the ability to fully incorporate the advice. Lifestyle recommendations are highly appreciated by patients but are still underutilized since they are offered mostly in the context of illness. The health calendar was shown to be useful to complement health intervention programs at the community level. The findings of our study underscore the acknowledged value of HRA by participants to tackle the risk factors of chronic diseases. If properly used HRA constitutes a simple and highly valued tool to help address patient's needs to prevent and control NCD in Argentina.

Preferences and satisfaction of IBD patients after switching from adalimumab 40 mg weekly to 80 mg every other week given as a single injection: the ADASCAL study.

BACKGROUND: A recently registered device containing 80 mg of adalimumab (ADA) allows an alternative dose escalation regimen with ADA 80 mg every other week (EOW) given as a single subcutaneous injection instead of 40 mg every week. The ADASCAL study evaluated the preferences and satisfaction of inflammatory bowel disease (IBD) patients after switching their ADA regimen from 40 mg weekly to 80 mg EOW given with a single-dose pen. METHODS: In this multicentre cross-sectional study, patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW completed the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4), a four-item questionnaire [a Likert-type 5-point scale for preferences, two closed questions for convenience and a 100-point visual analogue scale (VAS) to assess which escalated ADA regimen patients would prefer to continue] and two Health-Related Quality of Life (HRQoL) questionnaires: the generic European Quality of Life-5 Dimensions (EQ-5D) and disease-specific Spanish version of the Inflammatory Bowel Disease Questionnaire (SIBDQ-9). RESULTS: In total, 77 patients (64 Crohn's disease and 13 ulcerative colitis) were included. The TSQM score showed a notably high global satisfaction [83.4, standard deviation (SD) = 14.1] of patients with ADA 80 mg EOW given with a single-dose pen, with high TSQM scores for individual components: effectiveness (77.6, SD = 16.9), convenience (83.7, SD = 14.5) and side effects (86.1, SD = 23.4). Most of the patients (74%) preferred the ADA EOW regimen (59.7% had strong preference, 14.3% slight preference). ADA EOW interferes less with daily activity (59.7%) and with travel plans (81.8%). Most patients (77%) would prefer to continue with ADA EOW (mean VAS score of 84.7, SD = 24.1, where 100 indicates a preference for ADA EOW). Patients reported high HRQoL scores on both the EQ-5D (72.3, SD = 20.1) and SIBDQ-9 (75.1, SD = 14.7). CONCLUSION: IBD patients in whom the ADA regimen was changed from 40 mg weekly to 80 mg EOW reported a higher preference for the EOW regimen and therefore most decided to continue with a single self-injection EOW.

Innovation in IBD Care During the COVID-19 Pandemic: Results of a Cross-Sectional Survey on Patient-Reported Experience Measures.

BACKGROUND: The coronavirus 2019 (COVID-19) pandemic is a clinical situation that could be used as prototype for implementation of new systems of care. METHODS: This was a single-center, cross-sectional study. We evaluated the feasibility of a strategy based on the conversion of face-to-face visits to telephone consultations to manage IBD outpatients during the COVID-19 pandemic. A 4-item telephone survey (3 closed questions and a 100-point numeric description scale) was conducted to evaluate satisfaction of patients with telephone consultations. RESULTS: Between March 11 and April 8, 2020, 98% of the 216 scheduled face-to-face visits could be converted to telephone consultations, and we resolved an additional 162 urgent consultations by telephone. The rate of IBD-related hospitalization and visits to the emergency department decreased by 50% and 58%, respectively, compared with rates in the same period the previous year. The 4-item survey was conducted in 171 outpatients. In closed questions, patients reported a very high degree of satisfaction with telephone consultations, with no differences between scheduled (n = 123) and urgent consultations (n = 48; P = NS). The overall satisfaction rating with the telephone consultation evaluated with the numerical description scale was 94% and 93% for scheduled and urgent consultations, respectively (P < 0.82). Less than 20% of patients would have preferred a face-to-face visit to the telephone consultation at the time. CONCLUSIONS: A strategy based on the conversion of face-to-face visits to telephone consultations was able to guarantee a minimum standard quality of care during the COVID-19 pandemic. Patients reported a very high degree of satisfaction with telephone consultations.

Recurrent granulomatous cheilitis associated with Crohn's disease successfully treated with ustekinumab: case report and literature review.

Granulomatous cheilitis, characterized by persistent inflammation of the lips and a granulomatous histology, is sometimes associated with Crohn's disease and is a therapeutic challenge. Reported evidence indicates treatment with an anti-TNF agent (mainly infliximab) is the most recommended therapeutic option after failure of conventional treatments. The clinical case reported the effectiveness of ustekinumab, a monoclonal antibody against interleukins 12/23, to induce the remission of severe and recurrent granulomatous cheilitis in a patient with Crohn's disease.

Analysis of the electronic delocalization in some isoelectronic analogues of B12 doped with beryllium and/or carbon.

In the current work, a new family of isoelectronic analogues to B12 is reported. The construction of this family was performed through the isoelectronic substitution principle to generate species such as B11C+, B11Be-, B10BeC, B10C22+, B10Be22- B9Be2C-, and B9BeC2+. The search for the global minimum was realized by utilizing genetic algorithms, while the induced magnetic field, electronic localization function, magnetic current densities, and multicenter aromaticity criteria were calculated to understand their electronic delocalization. Our results show that, in general, C atoms avoid hypercoordination, whereas we have found species with Be atoms located in hypercoordinated positions that are relatively stable. Our analysis of aromaticity indicates that B12 has double σ and π disk aromaticity. Mono, double or triple substitution of B by C+ or Be- reduces somewhat the aromaticity of the clusters, but less in the case of Be- substitution.

2019 novel coronavirus disease (COVID-19) in patients with inflammatory bowel diseases.

BACKGROUND: Data on patients with inflammatory bowel diseases (IBD) who have had 2019 novel coronavirus (SARS-CoV-2) disease (COVID-19) are needed. AIMS: To report the clinical characteristics, including gastrointestinal symptoms, of COVID-19 in IBD patients, and to assess the risk of COVID-19 in IBD. METHODS: This case series included consecutive IBD patients with laboratory-confirmed COVID-19. Age-adjusted cumulative incidences were compared with the general population in the Madrid region. RESULTS: Through April 8, 12 of 1918 IBD patients were diagnosed with COVID-19. The average age was 52 years, 75% of the patients were female and 58.3% had Crohn's disease. Seven patients (58%) were on maintenance treatment with immunomodulators/biologics, of these four with combined therapy (33%). Eight patients (66%) required hospitalisation (one intensive care unit admission, and two deaths), and four patients were isolated at home. Nine patients had diarrhoea ranging between 4 and 10 loose stools per day (mean 5.4, SD 1.6). In five patients (42%) diarrhoea was a presenting symptom. In two patients, diarrhoea was the only symptom at debut. Cumulative incidence of COVID-19 was 6.2 per 1000 IBD patients. IBD patients had a lower adjusted incidence ratio of COVID-19 (OR 0.74, 95% CI 0.70-0.77; P < 0.001), and a similar associated mortality ratio (OR 0.95, 95% CI: 0.84-1.06; P = 0.36), compared with the general population. CONCLUSIONS: IBD patients do not have an increased risk of COVID-19 and associated mortality compared with the general population. In many IBD patients, diarrhoea was a presenting symptom, and sometimes, was the only symptom at onset of COVID-19.

Usefulness of monitoring antitumor necrosis factor serum levels during the induction phase in patients with Crohn's disease.

AIMS: The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. METHODS: Patients with Crohn's disease naïve to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score <150 after 14 weeks of treatment. Blood samples were obtained at baseline and at weeks 4, 8, and 14. Adalimumab and infliximab levels were measured, receiver operating characteristic (ROC) curves were constructed, and the area under the ROC curve was calculated. RESULTS: One-hundred fifty patients with Crohn's disease were included, 79 (53%) received infliximab and 71 (47%) had CDAI > 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 µg/mL, P > 0.05) or with and without response (7 vs. 11 µg/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 µg/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 µg/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. CONCLUSION: Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.