In recent years, powerful genetic code reprogramming methods have emerged that allow new functional components to be embedded into proteins as noncanonical amino acid (ncAA) side chains. In this ...review, we will illustrate how the availability of an expanded set of amino acid building blocks has opened a wealth of new opportunities in enzymology and biocatalysis research. Genetic code reprogramming has provided new insights into enzyme mechanisms by allowing introduction of new spectroscopic probes and the targeted replacement of individual atoms or functional groups. NcAAs have also been used to develop engineered biocatalysts with improved activity, selectivity, and stability, as well as enzymes with artificial regulatory elements that are responsive to external stimuli. Perhaps most ambitiously, the combination of genetic code reprogramming and laboratory evolution has given rise to new classes of enzymes that use ncAAs as key catalytic elements. With the framework for developing ncAA-containing biocatalysts now firmly established, we are optimistic that genetic code reprogramming will become a progressively more powerful tool in the armory of enzyme designers and engineers in the coming years.In recent years, powerful genetic code reprogramming methods have emerged that allow new functional components to be embedded into proteins as noncanonical amino acid (ncAA) side chains. In this review, we will illustrate how the availability of an expanded set of amino acid building blocks has opened a wealth of new opportunities in enzymology and biocatalysis research. Genetic code reprogramming has provided new insights into enzyme mechanisms by allowing introduction of new spectroscopic probes and the targeted replacement of individual atoms or functional groups. NcAAs have also been used to develop engineered biocatalysts with improved activity, selectivity, and stability, as well as enzymes with artificial regulatory elements that are responsive to external stimuli. Perhaps most ambitiously, the combination of genetic code reprogramming and laboratory evolution has given rise to new classes of enzymes that use ncAAs as key catalytic elements. With the framework for developing ncAA-containing biocatalysts now firmly established, we are optimistic that genetic code reprogramming will become a progressively more powerful tool in the armory of enzyme designers and engineers in the coming years.
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IJS, KILJ, NUK, PNG, UL, UM
Background & Aims Few data are available on effects of biologic therapies in patients more than 65 years old with inflammatory bowel disease (IBD). We evaluated the risk and benefits of therapy with ...tumor necrosis factor (TNF) inhibitors in these patients. Methods We collected data from patients with IBD treated with infliximab (n = 2475) and adalimumab (n = 604) from 2000 to 2009 at 16 tertiary centers. Ninety-five patients (3%) were more than 65 years old (52 men; 37 with ulcerative colitis and 58 with Crohn's disease; 78 treated with infliximab and 17 with adalimumab). The control group comprised 190 patients 65 years old or younger who were treated with both biologics and 190 patients older than 65 years who were treated with other drugs. The primary end points were severe infection, cancer, or death. Results Among patients more than 65 years old who received infliximab and adalimumab, 11% developed severe infections, 3% developed neoplasms, and 10% died. No variable was associated with severe infection or death. Among control patients more than 65 years old, 0.5% developed severe infections, 2% developed cancer, and 2% died. Among control patients less than 65 years old, 2.6% developed severe infections, none developed tumors, and 1% died. Conclusions Patients older than 65 years treated with TNF inhibitors for IBD have a high rate of severe infections and mortality compared with younger patients or patients of the same age that did not receive these therapeutics. The effects of anti-TNF agents in older patients with IBD should be more thoroughly investigated, because these patients have higher mortality related to hospitalization than younger patients.
Abstract The two main forms of intestinal bowel disease, namely ulcerative colitis and Crohn’s disease, are not curable but can be controlled by various medical therapies. The Italian Group for the ...Study of Inflammatory Bowel Disease (IG-IBD) has prepared clinical practice guidelines to help physicians prescribe corticosteroids and immunosuppressive drugs for these patients. The guidelines consider therapies that induce remission in patients with active disease as well as treatment regimens that maintain remission. These guidelines complement already existing guidelines from IG-IBD on the use of biological drugs in patients with inflammatory bowel diseases.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract Background Late-onset UC represents an important issue for the near future, but its outcomes and relative therapeutic strategies are yet poorly studied. Aim To better define the natural ...history of late-onset ulcerative colitis. Methods In a multicenter retrospective study, we investigated the disease presentation and course in the first 3 years in 1091 UC patients divided into 3 age-groups: diagnosis ≥65 years, 40–64 years, and <40 years. Disease patterns, medical and surgical therapies, and risk factors for disease outcomes were analyzed. Results Chronic active or relapsing disease accounts for 44% of patients with late-onset UC. Across all age-groups, these disease patterns require 3–6 times more steroids than remitting disease, but immunomodulators and, to a lesser extent, biologics are less frequently prescribed in the elderly. Advanced age, concomitant diseases and related therapies were found to be inversely associated with the use of immunomodulators or biologics, but not with surgery. Conclusions The conclusion that late-onset UC follows a mild course may apply only to a subset of patients. an important percentage of elderly patients present with more aggressive disease. Since steroid use and surgery rates did not differ in this subgroup, lower use of immunosuppressive therapy and biologics may reflect concerns in prescribing these therapies in the elderly.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
ObjectiveHeterogeneity among clinical presentation can cause difficulties when diagnosing SLE. One of the most specific immunologic criteria for this disease are anti-dsDNA antibodies. However, to ...detect these autoantibodies, different test methods are offered. This study will compare sensitivity of ELISA and EliA by synchronous testing in SLE patients.MethodsBetween March and August 2022 samples from (suspected) SLE patients, undergoing anti-dsDNA testing, were simultaneously measured by dsDNA/nucleosome ELISA (positive IU/ml >100) and dsDNA EliA (positive > 15 IU/ml). SLICC 2012 classification criteria were used to include SLE patients. Clinical data including clinical SLEDAI-2K were retrospectively retrieved from medical records.ResultsOut of 163 tested patients, 143 SLE patients were eligible for study analysis. Demographic characteristics are summarized in table 1. Sensitivity was 88.4% for ELISA versus 63.0% in EliA (McNemar. p<0.001). Of 13/14 patients with EliA+/ELISA- discrepancy (median SLEDAI 0.5), ELISA had been positive in the past. Median SLEDAI was higher for patients with EliA-/ELISA+ discrepancy (see table 2).ConclusionsIn our SLE cohort, there was a striking difference in sensitivity between anti-dsDNA test results (mainly EliA-/ELISA+ discrepancy) despite active disease in these patients. We hypothesize that this might be explained by the presence of anti-nucleosome antibodies, which can be detected by dsDNA/nucleosome ELISA or ENA-immunoblot. Clinicians should be aware of lower sensitivity (higher chance of false negatives) in EliA when interpreting anti-dsDNA test results.Abstract P12 Table 1Demographic characteristics N (%) Median (IQR) Sex Male 15 (10.3%) Female 131 (89.7%) Age in years (at time of testing) 38 (25–49) Disease duration in months 131 (31–205) Treatment (at time of testing) No 17 (11.6%) Yes 129 (88.4%) Abstract P12 Table 2EliA vs. ELISA test results and median SLEDAI (IQR) per subgroup ELISA + ELISA - Total EliA + NMedian SLEDAI (IQR) 787.5 (2.0–10.0) 140.5 (0.0–2.0) 92 EliA - NMedian SLEDAI (IQR) 517.0 (5.0–12.0) 30 (0–0) 54 Total 129 17 146
Abstract Background and aims The effectiveness of adalimumab in the treatment of ulcerative colitis is under debate. Although controlled trials have shown that adalimumab is significantly better than ...placebo, the absolute clinical benefit is modest. We report data on the effectiveness of adalimumab in a cohort of ulcerative colitis patients treated in 22 Italian centres. Methods All patients with active disease treated with adalimumab were retrospectively reviewed. Co-primary endpoints were clinical remission at weeks 4, 12, 24 and 54. Secondary endpoints were sustained clinical remission, steroid discontinuation, endoscopic remission and need for colectomy. Results Eighty-eight patients were included. Most patients had received previous infliximab treatment. Clinical remission rates were 17%, 28.4%, 36.4% and 43.2% at 4, 12, 24 and 54 weeks respectively. Twenty-two patients required colectomy. Clinical remission and low C-reactive protein at week 12 predicted clinical remission at week 54 (OR 4.17, 95% CI 2.36–19.44; OR 2.63, 95% CI 2.32–14.94, respectively). Previous immunosuppressant use was associated with a lower probability of clinical remission at week 54 (OR 0.67, 95% CI 0.08–0.66) and with a higher rate of colectomy (HR 9.7, 95% CI 1.46–9.07). Conclusion In this large “real-life” experience adalimumab appears effective in patients with otherwise medically refractory ulcerative colitis. Patients achieving early remission can expect a better long-term outcome.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic ...manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring
interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice.
Background and Aims:
Cancer risk in inflammatory bowel disease IBD is still debated. In a prospective, multicentre, nested case-control study, we aimed to characterise incident cases of cancer in ...IBD. The role of immunomodulators vs clinical characteristics of IBD as risk factors for cancer was also investigated.
Materials and Methods:
From January 2012 to December 2014, each IBD patient with incident cancer was matched with two IBD patients without cancer for: IBD type, gender, and age. Risk factors were assessed by multivariate regression analysis.
Results:
IBD patients considered numbered 44619: 21953 Crohn’s disease CD, 22666 ulcerative colitis UC. Cancer occurred in 174 patients: 99 CD CD-K, 75 UC UC-K. Controls included 198 CD CD-C, 150 UC UC-C. Cancer incidence in IBD was 3.9/1000, higher in CD (4.5/1000 99/21,953) than in UC (3.3/1000 75/22,666; p = 0.042). Cancers involved: digestive system 36.8%, skin 13.2%, urinary tract 12.1%, lung 8.6%, breast 8%, genital tract 6.9%, thyroid 4.6%, lymphoma 3.5%, others 6.3%. In CD, penetrating behaviour and combined thiopurines and tumour necrosis factor alpha TNFα antagonists were risk factors for cancer overall: odds ratio OR (95% confidence interval CI 2.33 1.01–5.47); 1.97 1.1–3.5; and for extracolonic cancers 3.9 1.56–10.1; 2.15 1.17–4.1, respectively. In UC, risk factors were pancolitis and disease-related surgery for cancer overall (OR: 2.52 1.26–5.1; 5.09 1.73–17.1); disease-related surgery for colorectal cancer CRC (OR 3.6 1.0–12); and extensive and left-sided vs distal UC for extracolonic cancers (OR: 2.55 1.15–5.9; 2.6 1.04–6.6), respectively.
Conclusions:
In a multicentre study, penetrating CD and extensive UC were risk factors for cancer overall. Cancer incidence was higher in CD than in UC.
Eleven known species of Monogenoidea were found parasitizing six different species of scombrid fishes collected from Rio de Janeiro coast, Southwestern Atlantic Ocean: Capsala biparasitica, Capsala ...katsuwoni, Capsala notosinense, Nasicola brasiliensis, Nasicola klawei, Allopseudaxinoides euthynni, Sibitrema poonui, Hexostoma albsmithi, Hexostoma euthynni, Hexostoma keokeo and Hexostoma sibi. Katsuwonus pelamis is reported as a new host to A. euthynni and Thunnus obesus to H. albsmithi. Capsala notosinense, A. euthynni, H. albsmithi and H. sibi are referred for the first time in Brazil, Southwestern Atlantic Ocean. Morphological and morphometric features are presented for each species.
Abstract Background Non-variceal upper gastrointestinal bleeding (NVUGIB) is an important cause of mortality and morbidity worldwide. Little information is available on the clinical management of ...non-variceal upper gastrointestinal bleeding in Italy in relation to the current organization of the Italian Emergency Health Services into Level-I and Level-II Emergency Departments (ED), the latter being more complex structures with greater resources. Methods A retrospective survey on clinical, endoscopic, and survival data was conducted by the regional sections of the 3 main Italian gastroenterological societies, AIGO, SIED and SIGE, recording all consecutive episodes of non-variceal upper gastrointestinal bleeding referred to 7 centres (4 of which were Level-II Emergency Departments) in Rome, Italy, during a one-year period. A total of 624 consecutive patients (64% males, mean age 67.6 ± 16.2 years) were included. Thirty-day mortality was 4.6%. Main factors associated with survival at both univariate and multivariate analysis were the presence of full Rockall score <5 and the admission to a Level-II Emergency Departments ( p < 0.001). Level-I Emergency Departments admitted patients with a full Rockall score ≥5 ( p = 0.02) more frequently than patients with negative endoscopic findings ( p < 0.001). Conclusions Referral of non-variceal upper gastrointestinal bleeding patients to Emergency Departments with more resources (Level-II) is associated with reduced mortality. Yet, unfortunately, high-risk patients were more often admitted to Level-I Emergency Departments, which suggests the need for a better organization of the emergency referral system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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