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The term Advanced Combination Treatment (ACT) involves the combination of at least two biologics or the use of a biologic with a small molecule drug, each with different mechanisms of action. This narrative review evaluates the current evidence supporting ACT in inflammatory bowel disease (IBD), focusing on preclinical studies, real-world evidence, and randomized controlled trials. A systematic review of randomized controlled trials has concluded that ACT significantly improves clinical outcomes, without significant safety concerns in patient with IBD. However, variability in trial designs and the lack of standardized outcome measures have led to initiatives aimed at mitigating these issues through a clear expert consensus. While the evidence for ACT in IBD is compelling, substantial challenges remain in standardizing treatment protocols and ensuring long-term safety. In the meantime, the use of ACT in clinical practice remains off-label and requires careful consideration of patient-specific factors. Future clinical trials should consider robust biomarkers for patient selection and leverage mechanistic insights to select combination components.

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ABSTRACTIntroduction: Treatment of ulcerative colitis (UC) aims to control symptoms and to suppress intestinal inflammation. Despite considerable advances, a proportion of patients do not respond to currently available drugs. The interleukin (IL)-23 axis plays a significant role in the pathogenesis of UC and has thus become an important target for drug development.Areas covered: The review briefly summarizes the pathophysiology of the IL-12/23 axis and provides a synopsis of the available evidence for efficacy and safety of ustekinumab, mirikizumab (LY3074828), risankizumab (BI655066/ABBV066), brazikumab (MEDI2070; formerly AMG139) and guselkumab (CNTO1959) in UC. We also provide an overview of ongoing and anticipated trials in this field.Expert opinion: A Phase 2 trial with mirikizumab and a Phase 3 trial with ustekinumab have demonstrated the efficacy of anti-IL-23 agents in achieving clinical and endoscopic outcomes in UC with a favorable safety profile. Trials of other anti-IL-23 agents in UC are under way and designed to explore head-to-head efficacy with existing biologics, as well as the prospect of combination biological therapy. Apart from data on longer term efficacy and safety, future trials should also explore strategies to inform the positioning of IL-23 antagonists in therapeutic algorithms.

The relationship between vedolizumab trough levels and combined endoscopic and clinical remission is unknown. To compare vedolizumab trough levels in patients with and without combined remission within the first year of treatment. We prospectively collected vedolizumab trough levels in 51 consecutive patients (28 Crohn's disease (CD) and 23 ulcerative colitis (UC)) before all infusions up to week 22, and at weeks 38 and 54, with concentrations measured after study completion. Centrally read endoscopy was performed at a median of 46 weeks. The primary outcome was combined endoscopic (CD: Simple endoscopic score for CD (SES-CD)?

Background The relationship between vedolizumab trough levels and combined endoscopic and clinical remission is unknown.Objective To compare vedolizumab trough levels in patients with and without combined remission within the first year of treatment.Methods We prospectively collected vedolizumab trough levels in 51 consecutive patients (28 Crohn's disease (CD) and 23 ulcerative colitis (UC)) before all infusions up to week 22, and at weeks 38 and 54, with concentrations measured after study completion. Centrally read endoscopy was performed at a median of 46 weeks. The primary outcome was combined endoscopic (CD: Simple endoscopic score for CD (SES-CD) < 4 without ulceration; UC: Mayo endoscopic subscore ≤ 1) and clinical remission (CD: resolution of abdominal pain; UC: resolution of rectal bleeding; both: resolution of altered bowel habit).Results Median vedolizumab trough levels at weeks 6 (25.7 vs 15.6 µg/mL; P= 0.015) and 22 (15.1 vs 4.9 µg/mL; P= 0.001) were higher in patients with combined remission. A threshold of 22 µg/mL at week 6 (area under the curve (AUC) 0.733; 95% confidence interval 0.567–0.899) and 8 µg/mL at week 22 (AUC 0.819; 95% confidence interval 0.692–0.946) predicted combined remission.Conclusion Early vedolizumab trough levels predicted combined endoscopic and clinical remission highlighting their possible use in clinical practice.

This report by the Slovenian Rarities Committee presents records of rare bird species in Slovenia in 2017, with some addenda for previous years. The numbers in brackets refer to the number of records (first number) and individuals (second number) recorded between 1 Jan 1950 and 31 Dec 2016. Since 1 Jan 2013, submission to the Committee has been required for 37 additional species, 17 of which are regional rarities. Records of these species are not numbered, since records from previous years were not collected by the Committee. The Barnacle Goose Branta leucopsiswas first recorded in Category A, in addition to previous Category D and E records. Other notable observations were the third record of Red-breasted Goose Branta ruficollis, fifth records of Lammergeier Gypaetus barbatusand Pomarine Skua Stercorarius pomarinus, and seventh records of Greater Blackbacked Gull Larus marinusand Red Phalarope Phalaropus fulicarius. The list of birds recorded in Slovenia (as of 31 Dec 2017) contains 390 species (375 in Category A, 6 in Category B, 9 exclusively in Category C; 4 species are both in Categories A and C). Category D contains 7 species, while Category E contains 39, two of which are classified into Subcategory E*. These two categories are not part of the list.

This report by the Slovenian Rarities Committee presents records of rare bird species in Slovenia in 2016, with some addenda for previous years. The numbers in brackets refer to the number of records (first number) and individuals (second number) recorded between 1 Jan 1950 and 31 Dec 2015. Since 1 Jan 2013, submission to the Committee has been required for 37 additional species, 17 of which are regional rarities. Records of these species are not numbered, since records from previous years were not collected by the Committee. Two new species, Scopoli’s Shearwater Calonectris diomedea and Arctic Tern Sterna paradisaea, were added to Category A. Other notable observations were the second record of Lesser Yellowlegs Tringa flavipes, third and fourth records of Pallid Swift Apus pallidus, fifth to seventh records of Long-legged Buzzard Buteo rufinus and the sixth and seventh records of Gannet Morus bassanus. Twelve records of Pallid Harrier Circus macrourus are an all-time annual high. Among Category E species, the Hooded Merganser Lophodytes cucullatus was recorded for the second time. The list of birds recorded in Slovenia (as of 31 Dec 2016) contains 388 species (373 in Category A, 6 in Category B, 9 exclusively in Category C; 4 species are both in Categories A and C). Category D contains 6 species, while Category E contains 38, two of which are classified into Subcategory E*. These two categories are not part of the list.

This report by the Slovenian Rarities Committee presents records of rare bird species in Slovenia in 2015, with some addenda for previous years. The numbers in brackets refer to the number of records (first number) and individuals (second number) recorded between 1 Jan 1950 and 31 Dec 2014. Since 1 Jan 2013, submission to the Committee has been required for 37 additional species, 17 of which are regional rarities. Records of these species are not numbered, since records from previous years were not collected by the Committee. One new species, the Desert Wheatear Oenanthe deserti, was added to category A. Other notable observations were the first record of Parrot Crossbill Loxia pytyopsittacus after 1909, the second record of Baillon’s Crake Zapornia pusilla, the third and fourth records of Calandra Lark Melanocorypha calandra, the fourth of Long-legged Buzzard Buteo rufinus, the fifth of Richard’s Pipit Anthus richardi and the sixth of Grey Phalarope Phalaropus fulicarius. Four species were added to category E: Bahama Pintail Anas bahamensis, Rosy-billed Pochard Netta peposaca, Harris’s Hawk Parabuteo unicinctus and Alexandrine Parakeet Psittacula eupatria. The list of birds recorded in Slovenia (as of 31 Dec 2015) contains 386 species (371 in category A, 6 in category B, 9 exclusively in category C; 4 species are both in categories A and C). Category D contains 6 species, while category E contains 38, two of which are classified into subcategory E*. These two categories are not part of the list.

This report by the Slovenian Rarities Committee presents records of rare bird species in Slovenia in 2014, with some addenda for previous years. The numbers in brackets refer to the number of records (first number) and individuals (second number) recorded between 1 Jan 1950 and 31 Dec 2013. Since 1 Jan 2013, submission to the Committee has been required for 37 additional species, 17 of which are regional rarities. Records of these species are not numbered, since records from previous years were not collected by the Committee. One new species was added to category C5: Sacred Ibis Threskiornis aethiopicus. One species, Spotted Dove Streptopelia chinensis, was added to category E. Breeding was confirmed for Muscovy Duck Cairina moschata and Northern Bobwhite Colinus virginianus; the two species were thus transferred to subcategory E*. Other notable observations were the third and fourth records of Black Vulture Aegypius monachus, fourth and fifth records of Gannet Morus bassanus, fourth record of Pomarine Skua Stercorarius pomarinus and fourth record of Richard’s Pipit Anthus richardi. The flocks of four Gannets and 23 Flamingos Phoenicopterus roseus have been the largest recorded in Slovenia to date. The list of birds recorded in Slovenia (as of 31 Dec 2014) contains 385 species (369 in category A, 7 in category B, 9 exclusively in category C; 4 species are both in categories A and C). Category D contains 6 species, while category E contains 34, two of which are classified into subcategory E*. These two categories are not part of the list.