The role of new inflammatory indices in the prediction of endoscopic and histological activity in inflammatory bowel disease patients.

BACKGROUND AND AIM: Inflammatory indices are promising indicators that can be used to evaluate inflammation in inflammatory bowel diseases (IBDs). The present study aimed to investigate the test accuracy of several inflammatory indices to identify endoscopic, and histological activity in a cohort of IBD patients. STUDY: All IBD patients who underwent colonoscopy and blood examination (within 4 weeks and without therapeutic change) were included. For these patients, 10 different inflammatory biomarkers were collected. Our primary outcome was the assessment of accuracy [evaluated with a receiver operating characteristics (ROC) analysis] of each inflammatory biomarker and indices. Furthermore, we tried to establish the optimal cutoff to identify patients with endoscopic and histologic activity among the inflammatory biomarkers and indices with higher performance. RESULTS: Regarding endoscopic activity, at the ROC analysis, the systemic inflammation response index (SIRI) showed the best accuracy [area under the curve (AUC), 0.627; confidence interval (CI), 0.552-0.698]. Whereas the ROC analysis showed a suboptimal AUC for the neutrophil-to-lymphocytes ratio (NLR) and platelets-to-lymphocytes ratio; (AUC, 0.620; CI, 0.545-0.691 and AUC, 0.607; CI, 0.532-0.679, respectively). Concerning histological activity, the C-reactive protein albumin ratio (CAR) presented a higher accuracy among the calculated inflammatory biomarkers (AUC, 0.682; CI, 0.569-0.781) while SIRI and NLR presented a subdued diagnostic performance. CONCLUSION: SIRI and CAR presented the best test accuracy in an IBD outpatient setting to identify endoscopic and histological activity. However, the test accuracy of all the evaluated Inflammatory indices appeared suboptimal. Fecal calprotectin has still the highest accuracy in predicting endoscopic and histological activity in patients with IBD.

IBD Patients with Primary or Secondary Nonresponse to Ustekinumab Benefit from Dose Escalation or Reinduction.

Ustekinumab is a monoclonal antibody approved for the treatment of IBD. This drug has a well-established efficacy; however, patients may not respond or lose response. The availability of other biological therapies prompts the need for comparative data between different agents to suggest first- or second-line strategies. Aim of this review is to compare the effectiveness of ustekinumab to other biologics in Crohn's disease and ulcerative colitis, as well as report the available data on dose escalation and reinduction. A systematic electronic search of the English literature was performed up to November 2023, using Medline (PubMed), Web of Science, Scopus and the Cochrane Library. Conference proceedings were also screened. Out of 659 citations, 80 relevant articles were selected and included in the present narrative review. Head-to-head comparisons of different biological drugs are relatively scarce, mostly deriving from indirect comparison or retrospective studies. Overall available data indicate similar effectiveness in the treatment of IBD patients. Dose escalation and reinduction strategies are well documented, but the optimal treatment schedule is still to be defined. Response and remission rates vary in different studies, and a proportion of patients fail to achieve clinical and endoscopic outcomes. However, both approaches are effective and safe in nonresponders and secondary loss of response. IBD patients may benefit from dose escalation or reinduction. Both strategies prove effective in regaining response in a proportion of patients, avoiding unnecessary early switch. Head-to-head trials are still needed to determine the exact placement of this drug compared to other biologics.

COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.

Background: Since its first report in Wuhan, China, in December 2019, COVID-19 has become a pandemic, affecting millions of people worldwide. Although the virus primarily affects the respiratory tract, gastrointestinal symptoms are also common. The aim of this narrative review is to provide an overview of the pathophysiology and clinical manifestations of gastrointestinal COVID-19. Methods: We conducted a systematic electronic search of English literature up to January 2023 using Medline, Scopus, and the Cochrane Library, focusing on papers that analyzed the role of SARS-CoV-2 in the gastrointestinal tract. Results: Our review highlights that SARS-CoV-2 directly infects the gastrointestinal tract and can cause symptoms such as diarrhea, nausea/vomiting, abdominal pain, anorexia, loss of taste, and increased liver enzymes. These symptoms result from mucosal barrier damage, inflammation, and changes in the microbiota composition. The exact mechanism of how the virus overcomes the acid gastric environment and leads to the intestinal damage is still being studied. Conclusions: Although vaccination has increased the prevalence of less severe symptoms, the long-term interaction with SARS-CoV-2 remains a concern. Understanding the interplay between SARS-CoV-2 and the gastrointestinal tract is essential for future management of the virus.

Nutrition, Nutritional Status, Micronutrients Deficiency, and Disease Course of Inflammatory Bowel Disease.

During the disease course, most Inflammatory Bowel Disease patients present a condition of malnutrition, undernutrition, or even overnutrition. These conditions are mainly due to suboptimal nutritional intake, alterations in nutrient requirements and metabolism, malabsorption, and excessive gastrointestinal losses. A suboptimal nutritional status and low micronutrient serum levels can have a negative impact on both induction and maintenance of remission and on the quality of life of Inflammatory Bowel Disease patients. We performed a systematic review including all the studies evaluating the connection between nutrition, nutrition status (including undernutrition and overnutrition), micronutrient deficiency, and both disease course and therapeutic response in Inflammatory Bowel Disease patients. This systematic review was performed using PubMed/MEDLINE and Scopus. Four main clinical settings concerning the effect of nutrition on disease course in adult Inflammatory Bowel Disease patients were analyzed (induction of remission, maintenance of remission, risk of surgery, post-operative recurrence, and surgery-related complications). Four authors independently reviewed abstracts and manuscripts for eligibility. 6077 articles were found; 762 duplicated studies were removed. Out of 412 full texts analyzed, 227 were included in the review. The evidence summarized in this review showed that many nutritional aspects could be potential targets to induce a better control of symptoms, a deeper remission, and overall improve the quality of life of Inflammatory Bowel Disease patients.

Old and New Adjunctive Therapies in Celiac Disease and Refractory Celiac Disease: A Review.

Celiac disease (CD) is a chronic enteropathy caused by the ingestion of gluten in a genetically susceptible individual. Currently, a gluten-free diet (GFD) is the only recommended treatment. However, unintentional gluten ingestion or a persistent villous atrophy with malabsorption (regardless of a strict GFD) as in the case of Refractory Celiac Disease (RCD) represents a major issue. In this review, we have analysed and discussed data from both randomized controlled trials and observational studies concerning adjunctive therapies as well as novel therapies for the treatment of CD and RCD. The literature search was carried out through Medline and Scopus. In total, 2268 articles have been identified and 49 were included in this review (36 studies resulting from the search strategy and 13 from other sources). Today, GFD remains the only effective treatment, although steroids, mesalamine, and more recently biological therapies have found space in the complex management of RCD. Currently, studies evaluating the effectiveness of novel therapies are still limited and preliminary results have been controversial.

Effectiveness of Vitamin D Supplementation on Disease Course in Inflammatory Bowel Disease Patients: Systematic Review With Meta-Analysis.

BACKGROUND: The vitamin D role in bone metabolism is well known; however, recent evidence suggests the impact of vitamin D in immune modulation and its implications in immune-mediated diseases, including inflammatory bowel disease (IBD). METHOD: We performed a systematic review with meta-analysis by a specific protocol (PROSPERO: CRD42022311184; March 2022, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311184). Randomized clinical trials involving IBD patients treated with vitamin D supplementation, compared with placebo, that evaluated the risk of clinical relapse and disease activity were included. Literature search was performed using Medline, Scopus, and Cochrane CENTRAL through January 2022. RESULTS: Out of 1448 articles, 12 (11 full-texts and 1 abstract) were included. Seven randomized clinical trials reported data on the clinical relapse as dichotomous outcome, while 7 studies reported data on disease activity expressed as continuous variables. The pooled risk ratio of clinical relapse was 0.64 (95% confidence interval, 0.46-0.89; I2 = 25%) among 458 IBD patients. However, this seems to be solid only in Crohn's disease (CD) patients. In fact, only 2 studies, involving 67 patients with ulcerative colitis, were included in the analysis. CD patients in clinical remission had a strong significant risk reduction in clinical relapse (risk ratio, 0.47; 95% confidence interval, 0.27-0.82; I2 = 0%), suggesting that it could be a specific subgroup with maximum clinical benefit of vitamin D supplementation. CONCLUSIONS: This meta-analysis shows that vitamin D supplementation can reduce the risk of clinical relapse in IBD patients, especially in CD patients in clinical remission. In a subgroup analysis, it was not significant (due to small number of studies and low number of patients), and well-powered studies are needed, in particular for ulcerative colitis patients.

This article is a systematic review with meta-analysis of randomized clinical trials involving inflammatory bowel disease patients treated with vitamin D supplementation, compared with placebo. We aim to assess the risk of clinical relapse or disease activity among these patients.

The Hydroxyquinol Degradation Pathway in Rhodococcus jostii RHA1 and Agrobacterium Species Is an Alternative Pathway for Degradation of Protocatechuic Acid and Lignin Fragments.

Deletion of the pcaHG genes, encoding protocatechuate 3,4-dioxygenase in Rhodococcus jostii RHA1, gives a gene deletion strain still able to grow on protocatechuic acid as the sole carbon source, indicating a second degradation pathway for protocatechuic acid. Metabolite analysis of wild-type R. jostii RHA1 grown on medium containing vanillin or protocatechuic acid indicated the formation of hydroxyquinol (benzene-1,2,4-triol) as a downstream product. Gene cluster ro01857-ro01860 in Rhodococcus jostii RHA1 contains genes encoding hydroxyquinol 1,2-dioxygenase and maleylacetate reductase for degradation of hydroxyquinol but also putative mono-oxygenase (ro01860) and putative decarboxylase (ro01859) genes, and a similar gene cluster is found in the genome of lignin-degrading Agrobacterium species. Recombinant R. jostii mono-oxygenase and decarboxylase enzymes in combination were found to convert protocatechuic acid to hydroxyquinol. Hence, an alternative pathway for degradation of protocatechuic acid via oxidative decarboxylation to hydroxyquinol is proposed.IMPORTANCE There is a well-established paradigm for degradation of protocatechuic acid via the ß-ketoadipate pathway in a range of soil bacteria. In this study, we have found the existence of a second pathway for degradation of protocatechuic acid in Rhodococcus jostii RHA1, via hydroxyquinol (benzene-1,2,4-triol), which establishes a metabolic link between protocatechuic acid and hydroxyquinol. The presence of this pathway in a lignin-degrading Agrobacterium sp. strain suggests the involvement of the hydroxyquinol pathway in the metabolism of degraded lignin fragments.

Cobalt/Lewis Acid Catalysis for Hydrocarbofunctionalization of Alkynes via Cooperative C-H Activation.

A catalytic system comprising a cobalt-diphosphine complex and a Lewis acid (LA) such as AlMe3 has been found to promote hydrocarbofunctionalization reactions of alkynes with Lewis basic and electron-deficient substrates such as formamides, pyridones, pyridines and related azines, imidazo[1,2-a]pyridines, and azole derivatives through site-selective C-H activation. Compared with known Ni/LA catalytic systems for analogous transformations, the present catalytic systems not only feature convenient setup using inexpensive and bench-stable precatalyst and ligand such as Co(acac)3 and 1,3-bis(diphenylphosphino)propane (dppp) but also display distinct site-selectivity toward C-H activation of pyridone and pyridine derivatives. In particular, a completely C4-selective alkenylation of pyridine has been achieved for the first time. Meanwhile, the present catalytic system proved to promote exclusively C5-selective alkenylation of imidazo[1,2-a]pyridine derivatives. Mechanistic studies including DFT calculations on the Co/Al-catalyzed addition of formamide to alkyne have suggested that the reaction involves cleavage of the carbamoyl C-H bond as the rate-limiting step, which proceeds through a ligand-to-ligand hydrogen transfer (LLHT) mechanism leading to an alkenyl(carbamoyl)cobalt intermediate.