A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.

Ultraconserved Elements Improve the Resolution of Difficult Nodes within the Rapid Radiation of Neotropical Sigmodontine Rodents (Cricetidae: Sigmodontinae).

Sigmodontine rodents (Cricetidae, Sigmodontinae) represent the second largest muroid subfamily and the most species-rich group of New World mammals, encompassing above 410 living species and ca. 87 genera. Even with advances on the clarification of sigmodontine phylogenetic relationships that have been made recently, the phylogenetic relationships among the 12 main groups of genera (i.e., tribes) remain poorly resolved, in particular among those forming the large clade Oryzomyalia. This pattern has been interpreted as consequence of a rapid radiation upon the group entrance into South America. Here, we attempted to resolve phylogenetic relationships within Sigmodontinae using target capture and high-throughput sequencing of ultraconserved elements (UCEs). We enriched and sequenced UCEs for 56 individuals and collected data from four already available genomes. Analyses of distinct data sets, based on the capture of 4634 loci, resulted in a highly resolved phylogeny consistent across different methods. Coalescent species-tree-based approaches, concatenated matrices, and Bayesian analyses recovered similar topologies that were congruent at the resolution of difficult nodes. We recovered good support for the intertribal relationships within Oryzomyalia; for instance, the tribe Oryzomyini appears as the sister taxa of the remaining oryzomyalid tribes. The estimates of divergence times agree with the results of previous studies. We inferred the crown age of the sigmodontine rodents at the end of the Middle Miocene, while the main lineages of Oryzomyalia appear to have radiated in a short interval during the Late Miocene. Thus, the collection of a genomic-scale data set with a wide taxonomic sampling provided resolution for the first time of the relationships among the main lineages of Sigmodontinae. We expect the phylogeny presented here will become the backbone for future systematic and evolutionary studies of the group.[Coalescent; Muroidea; Oryzomyalia; phylogenomics; polytomy; Rodentia; Sigmodontalia; species tree; UCEs.].

Older Adult Patients Use More Aminosalicylate Monotherapy Compared With Younger Patients With Inflammatory Bowel Disease: TARGET-IBD.

GOAL: The goal of this study was to describe medication utilization patterns in older inflammatory bowel disease (IBD) patients. BACKGROUND: Despite a growing population of older patients with Crohn's disease (CD) and ulcerative colitis (UC), questions remain regarding medication utilization patterns in comparison to younger populations. MATERIALS AND METHODS: We collected data from the 34 sites in TARGET-IBD, a multicenter, observational cohort. The primary outcome in this study was the IBD-specific therapy utilized among older patients with IBD compared with younger age groups. Therapy use was analyzed using pairwise comparisons and then the odds of IBD-specific therapy use among patients older than age 65 were evaluated using multivariable logistic regression models. RESULTS: We identified 2980 patients with IBD (61% CD). In multivariable analysis, younger patients with UC were significantly less likely to utilize aminosalicylate monotherapy when compared with patients above 65 years [age 18 to 29: adjusted odds ratio (aOR)=0.51, 95% confidence interval (CI): 0.33-0.78]. In patients with CD, younger patients were significantly less likely to use aminosalicylate monotherapy when compared with patients above 65 (greatest difference age 18 to 29: aOR=0.31, 95% CI: 0.18-0.52). Younger patients with CD and UC were significantly more likely to use anti-tumor necrosis factor monotherapy than patients above 65 years (age 18 to 29: aOR=3.87, 95% CI: 2.47-6.06 and aOR=2.68, 95% CI: 1.29-5.58, respectively). CONCLUSIONS: Older patients with IBD demonstrate significant differences in medication utilization, including more aminosalicylate monotherapy and less anti-tumor necrosis factor monotherapy compared with younger age groups. Given the aging population in the United States, these utilization patterns may have long-term implications for disease control.

Objective disease activity assessment and therapeutic drug monitoring prior to biologic therapy changes in routine inflammatory bowel disease clinical practice: TARGET-IBD.

BACKGROUND: Inflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients. METHODS: TARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained. RESULTS: 525 patients (71.4% Crohn's disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18-39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01-2.50). CONCLUSION: Nearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.

Discovery of ß-N-acetylglucosaminidases from screening metagenomic libraries and their use as thioglycoligase mutants.

ß-N-Acetylhexosaminidases (HexNAcases) are versatile biocatalysts that cleave terminal N-acetylhexosamine units from various glycoconjugates. Established strategies to generate glycoside-forming versions of the wild type enzymes rely on the mutation of their catalytic residues; however, successful examples of synthetically useful HexNAcase mutants are scarce. In order to expand the range of HexNAcases available as targets for enzyme engineering, we functionally screened a metagenomic library derived from a human gut microbiome. From a pool of hits, we characterized four of the more active candidates by sequence analysis and phylogenetic mapping, and found that they all belonged to CAZy family GH20. After detailed kinetic analysis and characterization of their substrate specificities, active site mutants were generated which resulted in the identification of two new thioglycoligases. BvHex E294A and AsHex E301A catalyzed glycosyl transfer to all three of the 3-, 4- and 6-thio-N-acetylglucosaminides (thio-GlcNAcs) that were tested. Both mutant enzymes also catalyzed glycosyl transfer to a cysteine-containing variant of the model peptide Tab1, with AsHex E301A also transferring GlcNAc onto a thiol-containing protein. This work illustrates how large scale functional screening of expressed gene libraries allows the relatively rapid development of useful new glycoside-forming mutants of HexNAcases, expanding the pool of biocatalysts for carbohydrate synthesis.

Methotrexate Is Not Superior to Placebo in Maintaining Steroid-Free Response or Remission in Ulcerative Colitis.

BACKGROUND & AIMS: Parenteral methotrexate induces clinical remission but not endoscopic improvement of mucosal inflammation in patients with ulcerative colitis (UC). We performed a randomized, placebo-controlled trial to assess the efficacy of parenteral methotrexate in maintaining steroid-free response or remission in patients with UC after induction therapy with methotrexate and steroids. METHODS: We performed a 48-week trial, from February 2012 through May 2016, of 179 patients with active UC (Mayo score of 6-12 with endoscopy subscore ≥ 2) despite previous conventional or biological therapy. The study comprised a 16-week open label methotrexate induction period followed by a 32-week double-blind, placebo-controlled maintenance period. Patients were given subcutaneous methotrexate (25 mg/wk) and a 12-week steroid taper. At week 16, steroid-free responders were randomly assigned to groups that either continued methotrexate (25 mg/wk, n = 44) or were given placebo (n = 40) until week 48. We compared the efficacy of treatment by analyzing the proportion of patients who remained relapse free and were in remission at week 48 without use of steroids or other medications to control disease activity. RESULTS: Ninety-one patients (51%) achieved response at week 16, and 84 patients were included in the maintenance period study. During this period, 60% of patients in the placebo group (24/40) and 66% in the methotrexate group (29/44) had a relapse of UC (P = .75). At week 48, 30% of patients in the placebo group (12/40) and 27% of patients in the methotrexate group (12/44) were in steroid-free clinical remission without need for additional therapies (P = .86). No new safety signals for methotrexate were detected. CONCLUSIONS: Parenteral methotrexate (25 mg/wk) was not superior to placebo in preventing relapses of UC in patients who achieved steroid-free response during induction therapy. ClinicalTrials.gov, Number: NCT01393405.

Facile Formation of ß-thioGlcNAc Linkages to Thiol-Containing Sugars, Peptides, and Proteins using a Mutant GH20 Hexosaminidase.

Thioglycosides are hydrolase-resistant mimics of O-linked glycosides that can serve as valuable probes for studying the role of glycosides in biological processes. The development of an efficient, enzyme-mediated synthesis of thioglycosides, including S-GlcNAcylated proteins, is reported, using a thioglycoligase derived from a GH20 hexosaminidase from Streptomyces plicatus in which the catalytic acid/base glutamate has been mutated to an alanine (SpHex E314A). This robust, easily-prepared, engineered enzyme uses GlcNAc and GalNAc donors and couples them to a remarkably diverse set of thiol acceptors. Thioglycoligation using 3-, 4-, and 6-thiosugar acceptors from a variety of sugar families produces S-linked disaccharides in nearly quantitative yields. The set of possible thiol acceptors also includes cysteine-containing peptides and proteins, rendering this mutant enzyme a promising catalyst for the production of thio analogues of biologically important GlcNAcylated peptides and proteins.

Genome-Wide Association Study Identifies African-Specific Susceptibility Loci in African Americans With Inflammatory Bowel Disease.

BACKGROUND & AIMS: The inflammatory bowel diseases (IBD) ulcerative colitis (UC) and Crohn's disease (CD) cause significant morbidity and are increasing in prevalence among all populations, including African Americans. More than 200 susceptibility loci have been identified in populations of predominantly European ancestry, but few loci have been associated with IBD in other ethnicities. METHODS: We performed 2 high-density, genome-wide scans comprising 2345 cases of African Americans with IBD (1646 with CD, 583 with UC, and 116 inflammatory bowel disease unclassified) and 5002 individuals without IBD (controls, identified from the Health Retirement Study and Kaiser Permanente database). Single-nucleotide polymorphisms (SNPs) associated at P < 5.0 × 10-8 in meta-analysis with a nominal evidence (P < .05) in each scan were considered to have genome-wide significance. RESULTS: We detected SNPs at HLA-DRB1, and African-specific SNPs at ZNF649 and LSAMP, with associations of genome-wide significance for UC. We detected SNPs at USP25 with associations of genome-wide significance for IBD. No associations of genome-wide significance were detected for CD. In addition, 9 genes previously associated with IBD contained SNPs with significant evidence for replication (P < 1.6 × 10-6): ADCY3, CXCR6, HLA-DRB1 to HLA-DQA1 (genome-wide significance on conditioning), IL12B,PTGER4, and TNC for IBD; IL23R, PTGER4, and SNX20 (in strong linkage disequilibrium with NOD2) for CD; and KCNQ2 (near TNFRSF6B) for UC. Several of these genes, such as TNC (near TNFSF15), CXCR6, and genes associated with IBD at the HLA locus, contained SNPs with unique association patterns with African-specific alleles. CONCLUSIONS: We performed a genome-wide association study of African Americans with IBD and identified loci associated with UC in only this population; we also replicated IBD, CD, and UC loci identified in European populations. The detection of variants associated with IBD risk in only people of African descent demonstrates the importance of studying the genetics of IBD and other complex diseases in populations beyond those of European ancestry.

Characterization of genetic loci that affect susceptibility to inflammatory bowel diseases in African Americans.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci. METHODS: We recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed. RESULTS: The strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 × 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 × 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 × 10(-6)). Additional suggestive associations (P < 4.2 × 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 × 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 × 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate <1 × 10(-5)) in genes that encode members of the JAK-STAT, cytokine, and chemokine signaling pathways, as well those involved in pathogenesis of measles. CONCLUSIONS: In a genetic analysis of 3308 AA IBD cases and controls, we found that many variants associated with IBD in Caucasians also showed association evidence with these diseases in AAs; we also found evidence for variants and loci not previously associated with IBD. The complex genetic factors that determine risk for or protection against IBD in different populations require further study.

Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing.

The extent to which microorganisms impair wound healing is an ongoing controversy in the management of chronic wounds. Because the high diversity and extreme variability of the microbiota between individual chronic wounds lead to inconsistent findings in small cohort studies, evaluation of a large number of chronic wounds using identical sequencing and bioinformatics methods is necessary for clinicians to be able to select appropriate empiric therapies. In this study, we utilized 16S rDNA pyrosequencing to analyze the composition of the bacterial communities present in samples obtained from patients with chronic diabetic foot ulcers (N = 910), venous leg ulcers (N = 916), decubitus ulcers (N = 767), and nonhealing surgical wounds (N = 370). The wound samples contained a high proportion of Staphylococcus and Pseudomonas species in 63 and 25% of all wounds, respectively; however, a high prevalence of anaerobic bacteria and bacteria traditionally considered commensalistic was also observed. Our results suggest that neither patient demographics nor wound type influenced the bacterial composition of the chronic wound microbiome. Collectively, these findings indicate that empiric antibiotic selection need not be based on nor altered for wound type. Furthermore, the results provide a much clearer understanding of chronic wound microbiota in general; clinical application of this new knowledge over time may help in its translation to improved wound healing outcomes.

Bacterial community survey of Solenopsis invicta Buren (red imported fire ant) colonies in the presence and absence of Solenopsis invicta virus (SINV).

Insect bacterial symbionts contribute to many essential biological functions of their hosts and can also influence host fecundity and fitness. The physiological contribution symbionts provide can aid in immune response and xenobiotic detoxification. Both of these immune factors can directly impact strategies aimed at managing insect populations. One biological control strategy that shows promise in insects is the use of single-stranded RNA viruses within the group Dicistroviridae. The Solenopsis invicta Virus (SINV; Dicistroviridae), a ssRNA virus, has been proposed as a potential biological control agent for the urban pest S. invicta Buren or red imported fire ant (RIFA). SINV has been shown to be prevalent in RIFA populations of Texas and Florida; however, mortality is associated with high viral load. In other insect microbe systems, presence of particular bacteria induced resistance against Dicistrovirus. If this type of relationship is present in the RIFA-SINV system, their bacterial community could reduce the effectiveness of SINV as a biological control system. The advantage of 454 pyro-sequencing is that it enables classification of unculturable bacteria. This study examines the bacterial community in brood, workers, and reproductive cast members from colonies with and without SINV infection. Manipulation of the bacterial community may alter virus infection and replication within the mid-gut. Understanding the differences in the microbial community of ant colonies may provide insights that will refine current efforts designing control strategies for this important urban pest.

Uptake of heavy metals by some edible vegetables irrigated using wastewater: a preliminary study in Accra, Ghana.

The heavy metals (Fe, Zn, Pb, Ni, Cr, Co, and Cd) burden in wastewater, soil, and vegetable samples from a wastewater irrigated farm located at KorleBu, Accra has been investigated. Flame atomic absorption spectrometry after microwave digestion using a combination of HNO3, HCl, and H2O2 (for water), and HNO3 and HCl (for soil and vegetables). The mean concentrations (in milligrams per kilogram) of heavy metals in the soil samples were in the order of Fe (171 ± 5.22) > Zn (36.06 ± 4.54) > Pb (33.35 ± 35.62) > Ni (6.31 ± 8.15) > Cr (3.40 ± 3.63) > Co (1.36 ± 0.31) > Cd (0.43 ± 0.24), while the vegetables were in the order of Fe (183.11 ± 161.2) > Zn (5.38 ± 3.50) > Ni (3.52 ± 1.27) > Pb (2.49 ± 1.81) > Cr (1.46 ± 0.51) > Co (0.66 ± 0.25) > Cd (0.36 ± 0.15). The bioconcentration factors suggest environmental monitoring for the heavy metals as follows: Cd (0.828), Cr (0.431), Ni (0.558), Co (0.485), and Fe (1.067). Estimated daily intakes were very low for both children and adults except Fe (0.767 mg/kg/day) in children. The population that consume vegetables from the study area were, however, estimated to be safe based on the results obtained from the health risk index, which were all < <1. The sodium absorption ratio according to FAO (1985) classifications indicate that the wastewater in the study area is unsuitable for irrigation purposes.

Determination of some heavy metal levels in soft drinks on the Ghanaian market using atomic absorption spectrometry method.

Twenty-three soft drink samples (i.e., four pineapple-based fruit drinks, eight citrus-based fruit juices, one soya-based drink, three cola carbonated drinks, one apple-based fruit drink, and six cocktail fruit drinks) were randomly purchased from retail outlets in an urban market in Accra and analyzed for the concentrations of iron, cobalt, cadmium, zinc, lead, and copper using flame atomic absorption spectrometry. The mean concentration of iron and cadmium were 0.723 ± 0.448 mg/L and 0.032 ± 0.012 mg/L, respectively. The mean cobalt concentration was 0.071 ± 0.049 mg/L, while the mean Zn concentration in the samples was 0.060 ± 0.097 mg/L. The mean concentrations of Pb and Cu in the fruit juice samples were 0.178 ± 0.091 mg/L and 0.053 ± 0.063 mg/L respectively. About 78 % of the samples exceeded the United States Environmental Protection Agency (USEPA) maximum contaminant level of 0.3 mg/L prescribed for iron, whereas all the samples exceeded the USEPA maximum contaminant level of 0.005 mg/L prescribed for cadmium. About 91 % of the samples exceeded the EU maximum contaminant level prescribed for lead insoft drinks.

Genome Sequencing of Multiple Primary Lung Cancers Harbouring Mixed Histology and Spontaneously Regressing Small-Cell Lung Cancer.

Up to 15% of lung cancer patients present two or more anatomically separate primary lung lesions, known as multiple primary lung cancers (MPLCs). While surgical resection or stereotactic body radiation therapy (SBRT) is the standard of care for most early-stage lung cancer cases, this may not be an option for patients with widespread tumours, highlighting the need for the improved targeted management of MPLC patients, which remains challenging. Moreover, the spontaneous regression (SR) of small-cell lung cancer (SCLC) is rare, with only four cases accounted for between 1988 and 2018. We report a rare MPLC case harbouring the mixed histology of non-small-cell lung cancer adenocarcinoma (NSCLCa) and SCLC and the SR of SCLC without treatment. The patient was diagnosed in 2015 with MPLCs, identified as NSCLCa and SCLC. In 2016, a restaging PET/CT scan prior to the start of treatment showed SCLC SR. In 2018, a further tumour was detected in the patient's mandible, and a re-biopsy of the SCLC revealed histology consistent with NSCLCa. Whole-genome sequencing (WGS) analysis identified a high expression of programmed death ligand-1 (PDL-1) in the NSCLCa, which was treated with pembrolizumab. WGS revealed distinct genomic profiles and mutational mechanisms in MPLCs, suggesting the need for distinct targeted therapies to improve the management of MPLC patients and highlighting the importance of precision evaluation.

Extraintestinal Manifestations and Family History of Inflammatory Bowel Disease Increase the Risk of Pouchitis in a State-Level Epidemiology Study.

INTRODUCTION: Our understanding of the epidemiology of inflammatory conditions of the pouch and effectiveness of treatment is largely based on selected populations. We created a state-level registry to evaluate the incidence of pouchitis and the effectiveness of treatments used in an initial episode of pouchitis. METHODS: In a state-level retrospective cohort of all patients undergoing proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis between January 1, 2018, and December 31, 2020, we evaluated the incidence of pouchitis and compared the proportion of patients developing recurrent pouchitis and chronic antibiotic-dependent pouchitis according to initial antibiotic therapy. RESULTS: A total of 177 patients underwent surgery with 49 (28%) developing pouchitis within the 12 months after the final stage of IPAA. Patients with extraintestinal manifestations of inflammatory bowel disease (IBD) were significantly more likely to develop pouchitis within the first 12 months after IPAA (adjusted odds ratio 2.45, 95% confidence interval 1.03-5.81) after adjusting for family history of IBD (adjusted odds ratio 3.50, 95% 1.50-8.18). When comparing the proportion of patients who developed recurrent pouchitis or chronic antibiotic-dependent pouchitis with those who experienced an isolated episode of pouchitis, there were no significant differences among the initial antibiotic regimens used. DISCUSSION: In a state-level examination of outcomes after IPAA for ulcerative colitis, patients with extraintestinal manifestations of IBD were more likely to develop pouchitis; however, the initial antibiotic regimen chosen did not seem to affect long-term outcomes.

Clinical Long-Term Outcomes of Patient-Reported Outcomes in the Prospective Real-World Tofacitinib Response in Ulcerative Colitis Registry.

INTRODUCTION: We previously reported the results of tofacitinib induction therapy in the prospective multisite US real-world Tofacitinib Response in Ulcerative Colitis registry. We now assessed patient-reported outcomes (PROs) and predictors of success during tofacitinib maintenance therapy. METHODS: Tofacitinib Response in Ulcerative Colitis included 103 patients with refractory ulcerative colitis (UC); 67% had failed ≥ 2 biologics. Patients reported the Simple Clinical Colitis Activity Index (SCCAI), Patient-Reported Outcome Measurement Information System measures for anxiety, depression, social satisfaction, and adverse events between weeks 8 and 52 using a web-based system. Paired t test and P for trend were used to compare changes in PRO measures over time. Bivariate analyses and logistic regression models were used to determine factors associated with response (SCCAI <5) or remission (SCCAI <2) at week 52. RESULTS: Of 103 patients, 82.5% entered the maintenance phase and 43.7% remained on tofacitinib at week 52. Tofacitinib de-escalation to 5 mg BID occurred in 15% of patients. At week 52, 42.7% and 31.1% of all patients reported an SCCAI <5 and SCCAI ≤2, respectively. Normalization of bowel frequency, rectal bleeding, and urgency occurred in 79%, 61%, and 48% of patients remaining on maintenance therapy. Social satisfaction improved significantly ( P < 0.001), while anxiety and depression scores only numerically improved. No consistent predictors for tofacitinib long-term treatment efficacy were identified, and safety findings were consistent with the known safety profile of tofacitinib. DISCUSSION: Tofacitinib is an effective maintenance therapy in patients with refractory UC. Dose reductions infrequently occurred during maintenance. Unmet needs in UC maintenance include improvement of urgency and psychosocial factors (NCT03772145).

Clinical Decision Making in Inflammatory Bowel Disease Mimics: Practice Management from Inflammatory Bowel Disease LIVE.

Background: Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications. Methods: Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results: Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions: The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Improving access to specialist multidisciplinary palliative care consultation for rural cancer patients by videoconferencing: report of a pilot project.

PURPOSE: Palliative care (PC) and palliative radiotherapy (RT) consultation are integral to the care of patients with advanced cancer. These services are not universally available in rural areas, and travel to urban centers to access them can be burdensome for patients and families. The objectives of our study were to assess the feasibility of using videoconferencing to provide specialist multidisciplinary PC and palliative RT consultation to cancer patients in rural areas and to explore symptom, cost, and satisfaction outcomes. METHODS: The Virtual Pain and Symptom Control and Palliative Radiotherapy Clinic was piloted from January 2008 to March 2011. Cancer patients in rural northern Alberta attended local telehealth facilities, accompanied by nurses trained in symptom assessment. The multidisciplinary team at the Cross Cancer Institute in Edmonton was linked by videoconference. Team recommendations were sent to the patients' family physicians. Data were collected on referral, clinical, and consultation characteristics and symptom, cost, and satisfaction outcomes. RESULTS: Forty-four initial consultation and 28 follow-up visits took place. Mean Edmonton Symptom Assessment Scale scores for anxiety and appetite were statistically significantly improved at the first follow-up visit (p < 0.01 and p = 0.03, respectively). Average per visit savings for patients seen by telehealth versus attending the CCI were 471.13 km, 7.96 hours, and Cdn $192.71, respectively. Patients and referring physicians indicated a high degree of satisfaction with the clinic. CONCLUSION: Delivery of specialist multidisciplinary PC consultation by videoconferencing is feasible, may improve symptoms, results in cost savings to patients and families, and is satisfactory to users.