Clinical utility of C-reactive protein-to-albumin ratio in the management of patients with inflammatory bowel disease.

Background and Aim: C-reactive protein (CRP)-to-albumin ratio (CAR) is a novel score with prognostic value in inflammatory conditions. This study assessed the performance of CAR as an objective marker of disease activity and prediction of subtherapeutic infliximab trough levels in patients with inflammatory bowel disease (IBD). Methods: A retrospective study was conducted on three different patient cohorts with IBD: patients who had (i) fecal calprotectin (FC) measurements; (ii) Mayo Endoscopic Scores; and (iii) infliximab trough levels available. The relative performances of CAR, albumin, and CRP were compared in predicting disease activity (based on FC or Mayo Endoscopic Score) and infliximab trough levels. Results: In both the FC (n = 289) and endoscopy (n = 65) cohorts, albumin and CAR correlated with objective disease activity. CAR (area under the curve [AUC] 0.70) was only marginally better at detecting active disease, measured by FC, compared to CRP (AUC 0.68). A CAR >0.15 was able to detect Mayo 3 disease (AUC 0.83, sensitivity 81%, specificity 89%). Albumin (r = 0.38) and CAR (r = -0.42) correlated with infliximab trough levels (n = 204). The optimal CAR for detecting subtherapeutic infliximab trough levels was >0.08 (AUC 0.70, sensitivity 66%, specificity 64%). Both albumin and CAR were independent predictors of subtherapeutic infliximab trough levels but correlated poorly with infliximab trough levels longitudinally in the same patient. Conclusion: CAR was only a modest discriminator of subtherapeutic infliximab levels and offers little more than CRP in detecting active disease. CAR has potential to detect severe Mayo 3 disease and could be calculated in patients admitted with suspected acute severe ulcerative colitis.

Exploring the effect of region on diversity and composition of weed seedbanks in herbicide-resistant crop systems in the United States.

BACKGROUND: Soil seedbanks have been recognized as one of the crucial components of agricultural ecosystems. However, studies on the shift in structure and biodiversity of soil seedbanks in herbicide-resistant crop systems are limited, and a functional trait perspective of the soil seedbank is often overlooked. RESULTS: A 6 years experiment was conducted to investigate the roles of region, crop system, and weed management strategy on species richness, functional trait diversity, and composition of the weed seedbank. Species richness was different across the interaction of region and crop system, while functional trait diversity only showed difference across regions. Species and functional trait compositions were affected by the interaction of region and crop system. Specifically, the compositional difference among crop systems was mainly determined by the significant heterogeneity of group dispersion. CONCLUSION: Growers and practitioners should consider weed functional traits in developing lasting agricultural management strategies. Long-term weed research should draw attention to the impact of transgenic crop systems and specific management tactics on weed dispersal, functional composition, and resistance evolution of weed species in such agroecosystems. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Adalimumab Drug Levels at Secondary Loss of Response Do Not Predict Response to Dose-intensification in Crohn's Disease: A Retrospective, International Multicenter Study.

BACKGROUND: The exposure-response relationship is less established for adalimumab (ADA) compared with infliximab in inflammatory bowel disease (IBD). Evidence supporting therapeutic drug monitoring post dose-intensification of ADA is limited. We aimed to explore the association between ADA drug levels and Crohn's disease (CD) activity at loss of response, and at 6 and 12 months post dose-intensification. METHODS: We performed a retrospective study of adult patients with CD receiving dose-intensified weekly ADA following secondary loss of response at 3 tertiary centers across 5 years. ADA trough levels were analyzed using a drug-sensitive enzyme-linked immunosorbent assay at loss of response, and 6 and 12 months after dose-intensification. Rates of clinical remission, objective remission (C-reactive protein <5 mg/L, fecal calprotectin <150 µg/g, or absence of inflammation at endoscopy or imaging), and ADA failure were investigated. RESULTS: A total of 131 CD patients were included, with a median disease duration of 9 (interquartile range, 4-17) years. 51% were biologic exposed prior to ADA and 50% received concomitant immunomodulators. Baseline drug levels measured at secondary loss of response did not discriminate between subsequent responders and non-responders at either 6 or 12 months post dose-intensification. However, both higher drug levels at 6 and 12 months and a higher increment from baseline were associated with improved outcomes. On receiver-operating characteristic analyses, post-escalation ADA drug levels >10.7 µg/mL (area under the receiver-operating characteristic curve [AUROC], 0.66; P = .013) and >10.9 µg/mL (AUROC, 0.67; P = .032) were associated with objective remission at 6 and 12 months, respectively. CONCLUSIONS: Drug levels following dose-intensification rather than at the time of secondary loss of response were associated with subsequent CD remission.

Literature supporting therapeutic drug monitoring at secondary loss of response and post dose-intensification of adalimumab is limited. Adalimumab drug levels following dose-intensification rather than at the time of secondary loss of response are associated with subsequent Crohn's disease remission.

Leveraging natural history collections to understand the impacts of global change.

This joint Special Feature focuses on the contributions and potential of natural history collections to address global change questions.

Pharmacist-Driven Therapeutic Infliximab Monitoring at the Point of Care Using Rapidly Assessed Drug Levels in Patients with Inflammatory Bowel Disease.

BACKGROUND: Therapeutic monitoring of infliximab is limited by the time lag between drug-level measurement and dose adjustment, along with the cost of dose escalation. Strategies for dose reduction in stable patients on maintenance infliximab at supratherapeutic levels are uncertain. This study determined the feasibility of a pharmacist-driven strategy for immediate dose adjustment using a sliding scale at the point of care in stable patients with inflammatory bowel disease on maintenance therapy. METHODS: Adult patients with stable disease undergoing maintenance therapy with infliximab infusions, 5 mg/kg every 8 weeks, were prospectively studied. Trough drug levels were assessed by a rapid assay (and later by ELISA) at all infusions for up to 12 months with immediate but quantitatively small dose adjustment according to a sliding scale targeting a therapeutic range of 3-7 mcg/mL. Disease activity was assessed both clinically and biochemically. RESULTS: The rapid assay and ELISA detected similar infliximab levels, and the strategy added approximately 30 minutes to the duration of infusion events. Only 20% of 48 patients (77% with Crohn disease) had baseline trough infliximab concentrations within the therapeutic range. This value increased 3-fold after 24 and 48 weeks of interventions. One in 2 patients had baseline supratherapeutic levels, and most were brought into the therapeutic range without a discernible impact on disease activity by 1 dose adjustment, but 2 or 3 adjustments were generally needed for 29% of patients with subtherapeutic levels. Overall, drug costs were reduced by 4%. CONCLUSIONS: Immediate dose adjustment after infliximab rapid assay performed by a pharmacist using a sliding scale is a feasible strategy. Supratherapeutic infliximab levels can be safely and quickly brought into the therapeutic range using small dose adjustments without affecting disease activity, offsetting (at least partly) costs associated with dose escalation.

Early sonographic response to a new medical therapy is associated with future treatment response or failure in patients with inflammatory bowel disease.

OBJECTIVE: Gastrointestinal ultrasound (GIUS) accurately assesses inflammation and is responsive to changes in inflammatory bowel disease. This study aimed to determine the prognostic utility of sonographic response in the first 14 weeks of a newly-instituted therapy with therapeutic response at 46 weeks and to compare its performance with standard clinical assessment tools. METHODS: Patients with sonographic evidence of inflammation were assessed by GIUS, clinical activity, serum C-reactive protein and faecal calprotectin again 2, 6 and 14 weeks after commencing a new biologic or thiopurine. Treatment failure was defined as undergoing surgery, hospitalisation, escalation of dosage or introduction of new medication over 46-weeks' follow-up. Sonographic response was defined as a decrease in bowel wall thickness and improved vascularity. RESULTS: In 31 patients (median age 49 years, 74% Crohn's disease), sonographic response at 14 weeks [OR 19.3, 95% confidence interval (CI), 3.23-101.10; P = 0.0054] and faecal calprotectin (P = 0.018), but no clinical disease activity or C-reactive protein, were predictive of subsequent treatment response. Sonographic response alone was predictive at week 6 (P = 0.016), but not week 2. 16% reduction in bowel wall thickness at 6 weeks (area-under-the-receiver-operator-curve=0.86; P = 0.002; sensitivity 72%, specificity 90%), with similar performance for 10% at 14 weeks, was associated with treatment response. CONCLUSION: Sonographic response as early as 6 weeks after initiation of a new therapy may accurately predict treatment outcomes over 46 weeks and is superior to other markers used to monitor disease activity.

Femtosecond damage experiments and modeling of broadband mid-infrared dielectric diffraction gratings.

High peak and average power lasers with high wall-plug efficiency, like the Big Aperture Thulium (BAT) laser, have garnered tremendous attention in laser technology. To meet the requirements of the BAT laser, we have developed low-dispersion reflection multilayer dielectric (MLD) gratings suitable for compression of high-energy pulses for operations at 2 micron wavelength. We carried out 10000-on-1 damage tests to investigate the fluence damage thresholds of the designed MLD gratings and mirrors, which were found between 100-230 mJ/cm2. An ultrashort pulsed laser (FWHM = 53 fs, λ = 1.9 µm) operating at 500 Hz was used in the serpentine raster scans. The atomic force microscope images of the damage sites show blister formation of the underlying layers at lower fluences but ablation of the grating pillars at higher fluences. We simulated the dynamic electronic excitation in the MLD optics with a finite-difference in the time domain approach in 2D. The simulation results agree well with the LIDT measurements and the observed blister formation. This model is able to evaluate the absolute LIDT of MLD gratings.

Split-dose 1 L polyethylene glycol (PEG) with ascorbate is non-inferior to split-dose PEG with sodium picosulfate and magnesium citrate with similar tolerability: a randomized study.

BACKGROUND AND AIM: Post-marketing studies comparing low-volume polyethylene glycol (PEG)-based regimens are limited. This randomized study aimed to compare the efficacy and tolerability of a novel 1-L low-volume PEG-based preparation: 1 L PEG+Asc (PEG3350, sodium ascorbate, sodium sulfate, ascorbic acid, sodium chloride, and potassium chloride) with PEG+SPMC (PEG3350, sodium chloride, potassium chloride and sodium sulfate, sodium picosulfate, magnesium oxide, citric acid, and aspartame), prior to routine colonoscopy at an Australian tertiary referral center. METHODS: Outpatients undergoing colonoscopy were randomized to receive either split-dose 1 L PEG+Asc or split-dose PEG+SPMC. Bowel preparation quality using the Boston Bowel Preparation Scale (BPPS), modified Aronchick scores, procedure time, cecal intubation, and adenoma detection rates were recorded. Patient compliance and tolerability were captured using a standardized questionnaire. RESULTS: A total of 173 patients were randomized, of whom 164 completed the study and were allocated to 1 L PEG+Asc (n = 82) or PEG+SPMC (n = 82). Non-inferiority of 1 L PEG+Asc was demonstrated with 89% achieving successful preparation (total BPPS ≥6 and each sub-score ≥2) compared with 85.4% in the PEG+SPMC group, resulting in an estimated difference of 3.7% (95% CI -6.6% to 13.9%). The median BBPS was non-inferior in all colonic segments with 1 L PEG+Asc (BBPS 3 [interquartile range 2-3]) vs PEG+SPMC (BBPS 2 [interquartile range 2-3]). More 1 L PEG+Asc patients reported moderate to severe nausea (P = 0.028), but overall tolerability was similar. CONCLUSIONS: The quality of bowel preparation achieved with 1 L PEG+Asc is non-inferior to that with PEG+SPMC, with similar tolerability outcomes. Further studies are required in patients at risk of suboptimal bowel preparation.

The Hierarchy-of-Hypotheses Approach: A Synthesis Method for Enhancing Theory Development in Ecology and Evolution.

In the current era of Big Data, existing synthesis tools such as formal meta-analyses are critical means to handle the deluge of information. However, there is a need for complementary tools that help to (a) organize evidence, (b) organize theory, and (c) closely connect evidence to theory. We present the hierarchy-of-hypotheses (HoH) approach to address these issues. In an HoH, hypotheses are conceptually and visually structured in a hierarchically nested way where the lower branches can be directly connected to empirical results. Used for organizing evidence, this tool allows researchers to conceptually connect empirical results derived through diverse approaches and to reveal under which circumstances hypotheses are applicable. Used for organizing theory, it allows researchers to uncover mechanistic components of hypotheses and previously neglected conceptual connections. In the present article, we offer guidance on how to build an HoH, provide examples from population and evolutionary biology and propose terminological clarifications.

Early Assessment With Gastrointestinal Ultrasound in Patients Hospitalised for a Flare of Ulcerative Colitis and Predicting the Need for Salvage Therapy: A Pilot Study.

Approximately 30% of patients hospitalised with severe ulcerative colitis do not respond to corticosteroids, but the decision to introduce salvage therapy is delayed to at least the third day of treatment, according to the widely applied Oxford criteria to assess response. This pilot study aimed to determine if gastrointestinal ultrasound performed on admission can predict steroid-refractory disease. In 10 consecutive patients with severe ulcerative colitis, gastrointestinal ultrasound was performed within 24 h of admission. Six patients failed corticosteroids and required infliximab salvage therapy. Colonic bowel wall thickness was a median of 4.6 mm (range 4.2-5.6 mm) in those responding to steroids compared with 6.2 mm (6-7.9 mm) in those requiring salvage therapy (p = 0.009). Any colonic segment with a bowel wall thickness of >6 mm was associated with the need for salvage therapy (p = 0.033). Gastrointestinal ultrasound may provide an early indication of poor corticosteroid response and enable a timelier introduction of salvage therapy in patients with severe ulcerative colitis.

Efficacy of Cover Crops for Pollinator Habitat Provision and Weed Suppression.

Pollinator declines have been documented globally, but little information is available about native bee ecology in Midwestern U.S. agriculture. This project seeks to optimize pollinator support and weed suppression in a 3-yr crop rotation with a fallow growing season. During fallow, one of five cover crop treatments (T1: crimson, red, and ladino clover and Bob oats [Fabales: Fabaceae - Trifolium incarnatum L., Trifolium pratense L., Trifolium repens L., and Cyperales: Poaceae - Avena sativa]; T2: crimson clover and oats; T3: red clover and oats; T4: ladino clover and oats; T5: no cover crop; T6/control: winter wheat [Cyperales: Poaceae - Triticum aestivum] L.) was seeded in one-half of 25 agricultural fields, whereas wheat was left unharvested in the other half as a comparison. Treatments that provide season-long floral resources support the greatest bee diversity and abundance (T1), and treatments with red clover support declining (Hymenoptera: Apidae) Bombus species (T1 and T3). Late-season floral resources may be important, yet limited (T1 and T4), and some species of agricultural weeds provide floral resources. Floral diversity may be less important than flower abundance or timing for pollinator diversity (T1-T4). Weed diversity was greatest in the no cover crop treatment (T5), least in winter wheat (T6), and intermediate in cover crop treatments (T1-T4) with no differences in weeds of economic concern. Wheat suppresses weeds but does not provide floral resources for pollinators. These results may also be applicable to marginal lands taken out of cultivation or field margin pollinator plantings in a typical corn-soybean rotation. Floral resource availability across the landscape is critical to maintain pollinator diversity.

Adaptive genetic potential and plasticity of trait variation in the foundation prairie grass Andropogon gerardii across the US Great Plains' climate gradient: Implications for climate change and restoration.

Plant response to climate depends on a species' adaptive potential. To address this, we used reciprocal gardens to detect genetic and environmental plasticity effects on phenotypic variation and combined with genetic analyses. Four reciprocal garden sites were planted with three regional ecotypes of Andropogon gerardii, a dominant Great Plains prairie grass, using dry, mesic, and wet ecotypes originating from western KS to Illinois that span 500-1,200 mm rainfall/year. We aimed to answer: (a) What is the relative role of genetic constraints and phenotypic plasticity in controlling phenotypes? (b) When planted in the homesite, is there a trait syndrome for each ecotype? (c) How are genotypes and phenotypes structured by climate? and (d) What are implications of these results for response to climate change and use of ecotypes for restoration? Surprisingly, we did not detect consistent local adaptation. Rather, we detected co-gradient variation primarily for most vegetative responses. All ecotypes were stunted in western KS. Eastward, the wet ecotype was increasingly robust relative to other ecotypes. In contrast, fitness showed evidence for local adaptation in wet and dry ecotypes with wet and mesic ecotypes producing little seed in western KS. Earlier flowering time in the dry ecotype suggests adaptation to end of season drought. Considering ecotype traits in homesite, the dry ecotype was characterized by reduced canopy area and diameter, short plants, and low vegetative biomass and putatively adapted to water limitation. The wet ecotype was robust, tall with high biomass, and wide leaves putatively adapted for the highly competitive, light-limited Eastern Great Plains. Ecotype differentiation was supported by random forest classification and PCA. We detected genetic differentiation and outlier genes associated with primarily precipitation. We identified candidate gene GA1 for which allele frequency associated with plant height. Sourcing of climate adapted ecotypes should be considered for restoration.

Comparison of medium to long-term outcomes of acute severe ulcerative colitis patients receiving accelerated and standard infliximab induction.

INTRODUCTION: Accelerated dose infliximab (IFX) induction is associated with reduced short-term colectomy rate in acute severe ulcerative colitis (ASUC). Data on medium/long-term outcomes of this strategy are limited. AIMS: Evaluate medium/long-term outcomes in patients receiving IFX induction for ASUC, comparing accelerated dose (AD) and standard dose (SD) induction. METHODS: Retrospective study of consecutive patients admitted with corticosteroid-refractory ASUC in four tertiary referral centres within INITIative IBD research network (www.initiativeibd.ie). IFX rescue was given either as SD (weeks 0, 2, 6) or AD (<28 days) from January 2010 to September 2017. AD induction has been utilised in participating centres since 2014. Consequently SD patients were subdivided based on time period of IFX rescue: historical SD group (SD1) (2010-2013) and current SD group (SD2) (2014-2017). Primary endpoint was time to colectomy; secondary endpoint was time to IFX discontinuation if induction was complete. RESULTS: 145 patients received rescue IFX (AD=58, SD1=32, SD2=55). Disease severity at induction was comparable between AD and SD1 groups; however, SD2 group had less severe disease: median C-reactive protein (CRP) 39, 44 and 20 mg/L for AD, SD1 and SD2 groups, respectively (p=0.026, Kruskal-Wallis); median CRP: albumin ratio was 1.4, 1.8 and 0.6 (p=0.016). Median follow-up for AD, SD1 and SD2 groups was 1.6 (IQR 1.1-3.1), 4.9 (IQR 2.6-5.5) and 1.5 (IQR 0.9-2.3) years. Time to colectomy was shorter in SD1 (log rank p=0.0013); no significant difference in time to colectomy was observed comparing AD and SD2 groups (log rank p=0.32). 123 patients (84%) completed IFX induction and received maintenance therapy. Time to IFX discontinuation was shorter in SD1 (log rank p=0.009). CONCLUSION: Time to colectomy is significantly prolonged with use of AD IFX in selected ASUC patients with more severe disease. Historical use of standard IFX induction for all ASUC patients is associated with inferior long-term outcomes.

Review article: determination of the therapeutic range for therapeutic drug monitoring of adalimumab and infliximab in patients with inflammatory bowel disease.

BACKGROUND: Clinical application of therapeutic drug monitoring (TDM) to optimise anti-TNF therapies in patients with IBD depends upon target ranges. AIMS: To review methodology used to determine therapeutic ranges and critically compare and contrast its application to infliximab and adalimumab. METHODS: A systematic review was performed, and relevant literature was summarised and critically examined. RESULTS: Upper limits of the therapeutic range are determined by toxicity, a plateau response and cost. Lower limits are determined by optimal concentration on the target of action in vitro and/or in vivo, or by correlation of drug levels with clinical efficacy using area-under-receiver-operator-curve (AUROC) analysis. In 43 studies, there were huge variations in time at which infliximab and adalimumab levels were measured, the end-points used (clinical remission to mucosal healing), the clinical setting (active disease vs maintenance phase) and the reason for TDM (proactive vs reactive). In the maintenance phase for infliximab, lower trough limits 2.8-5.7 µg/mL are reported depending upon end-points used, with consistent AUROC 0.68-0.77. Adalimumab TDM targets are even less consistent with a lower limit 5.9-11.8 µg/mL (AUROC 0.66-0.83) in some studies, but no cut-off can be identified that is significantly associated with outcome in others, related to inherent pharmacokinetic and pharmacodynamic differences, and heterogeneity of study design. CONCLUSIONS: Evidence for exposure-response relationship is stronger for infliximab than adalimumab. Due to heterogeneity in settings for drug level measurements, therapeutic ranges vary. These factors need to be taken into account when interpreting the evidence and extending this to therapeutic strategies for IBD patients.

Do No Harm: Efficacy of a Single Herbicide Application to Control an Invasive Shrub While Minimizing Collateral Damage to Native Species.

Control of invasive exotic species in restorations without compromising the native plant community is a challenge. Efficacy of exotic species control needs to consider collateral effects on the associated plant community. We asked (1) if short-term control of a dominant exotic invasive, Lespedeza cuneata in grassland restorations allows establishment of a more diverse native plant community, and (2) if control of the exotic and supplemental seed addition allows establishment of native species. A manipulative experiment tested the effects of herbicide treatments (five triclopyr and fluroxypyr formulations plus an untreated control) and seed addition (and unseeded control) on taxonomic and phylogenetic diversity, and community composition of restored grasslands in three sites over three years. We assessed response of L. cuneata through stem density counts, and response of the plant community through estimates of canopy cover. Herbicide treatments reduced the abundance of the exotic in the first field season leading to a less dispersed community composition compared with untreated controls, with the exotic regaining dominance by the third year. Supplemental seed addition did not provide extra resistance of the native community to reinvasion of the exotic. The communities were phylogenetically over-dispersed, but there was a short-term shift to lower phylogenetic diversity in response to herbicides consistent with a decrease in biotic filtering. Native plant communities in these grassland restorations were resilient to short-term reduction in abundance of a dominant invasive even though it was insufficient to provide an establishment window for native species establishment.

Impact of a higher fecal immunochemistry test cut-off on pathology detected in subsequent rounds of a colorectal screening program.

BACKGROUND AND AIMS: Fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening is superior to the traditional binary fecal occult blood test. Its quantitative nature allows the investigator to choose a positivity threshold to match cost and endoscope capacity. The optimal threshold is still debated. BowelScreen, the Irish national colorectal cancer screening program, has a cut-off of 45 µg Hb/g feces, and in this study we investigated the impact of this threshold on pathology detected in round 2 in individuals who had a negative result for round 1 FIT (FIT1). METHODS: All individuals with a negative FIT1 result who completed a round 2 FIT (FIT2) 2 years later were included. Pathology outcomes for individuals who had positive FIT2 results were correlated with FIT1 levels. RESULTS: A total of 37,877 individuals had negative FIT1 results and completed FIT2. One thousand two hundred thirty (3.2%) had positive FIT2 results (702 men [57%], median age 69, age range 60-70 years). Quantitative analysis showed that at an FIT1 level <5 µg Hb/g feces, 2.3% had positive FIT2 results. At a higher cut-off of 40.1 to 45 µg Hb/g feces, 15.6% of individuals had positive FIT2 results. One thousand two (81.5%) underwent colonoscopy, with clinical outcomes in all cases. Three hundred fifty-one (35%) had normal colonoscopy results. The proportion of individuals with normal colonoscopy results decreased as FIT1 levels rose. Conversely, advanced pathology (CRC + high-risk adenomas) rates rose from 7% to 50% when FIT1 was <5 compared with 40.1 to 45 µg Hb/g feces, respectively. There were 51 screen-detected cancers in round 2 among individuals with negative FIT1 results (22 stage I, 12 stage II, 14 stage III, 3 stage IV). All 3 stage IV individuals had FIT1 results <20 µg Hb/g feces. CONCLUSIONS: Varying rates of pathology are observed in round 2 of a screening program based on the quantitative level of a negative round 1 FIT result when the positivity threshold is relatively high. A CRC rate of 5.1% within this group appears acceptable. Although patients with incurable cancer were observed, the positivity threshold to capture these cases within round 1 would have been so sensitive that it would create an unsustainable endoscopy referral burden.

A prospective study of faecal immunochemical testing following polypectomy in a colorectal cancer screening population.

INTRODUCTION: 52% of faecal immunohistochemistry test (FIT)-positive clients in the Irish National Colorectal Cancer Screening Programme (BowelScreen) have adenomatous polyps identified at colonoscopy in round 1. Although it is known that advanced adenomas and cancers cause an elevated FIT, it is not known if small (<5 mm) adenomas cause a positive FIT. AIMS: Determine if removal of small polyps in an FIT-based colorectal cancer (CRC) screening programme is associated with a negative FIT on follow-up. METHODS: A single-centre prospective observational study of consecutive participants attending for first round screening colonoscopy who had a positive FIT (>45 µg Hb/g) as part of the Irish Colorectal Cancer Screening Programme. Subjects were consented at the time of colonoscopy and were sent a repeat FIT 4-6 weeks later. Precolonoscopy and postcolonoscopy FITs were compared and correlated with clinical findings and endoscopic intervention. RESULTS: 112 consecutive first round participants were recruited. Eight (7%) had cancer, 75 (67%) adenomatous polyps, 17 (15%) a normal colonoscopy and 12 (11%) other pathology. There was a clear difference in median FIT levels between the four groups (P=0.006). Advanced pathology (tumour or adenomatous polyp >1 cm) was associated with higher FIT than non-advanced pathology (median FIT 346 vs 89 P=0.0003). 83% (86/104) of subjects completed a follow-up FIT. Follow-up FIT remained positive in 20% (17/86). Polypectomy was associated with a reduction in FIT from a median of 100 to 5 µg Hb/g (P<0.0001). Removal of polyps >5 mm was the only factor independently associated with a negative follow-up FIT on multivariate analysis (OR 3.9 (1.3-11.9, P=0.04)). CONCLUSION: FIT is a sensitive test and levels increase with advanced colonic pathology. Polypectomy of advanced adenomas is associated with a negative follow-up FIT. However, alternative causes for a positive FIT should be considered in patients who have adenomas less than 5 mm detected or a normal colonoscopy.

CRP/Albumin Ratio: An Early Predictor of Steroid Responsiveness in Acute Severe Ulcerative Colitis.

INTRODUCTION: Identifying hospitalized patients with acute severe ulcerative colitis (ASUC) who will be refractory to corticosteroid therapy and require rescue therapy remains difficult. Hypoalbuminemia worsens with time during hospitalization and is associated with rapid clearance of and reduced response to infliximab (IFX) rescue. Early use of rescue therapy may therefore be more effective. Simple clinical and laboratory predictors of corticosteroid responsiveness would facilitate earlier use of rescue therapy. MATERIALS AND METHODS: Retrospective study of a prospectively maintained database of 3600 patients attending a single center was conducted. Patients with histologically confirmed ulcerative colitis admitted with ASUC over a 5-year period from January 2010 to December 2014 were identified. All patients initially received intravenous corticosteroids. Patient demographics were collected; C-reactive protein (CRP) and albumin levels were recorded at baseline and during admission. Receiver operating characteristic statistics were used to determine the optimal stool frequency, CRP, albumin, and CRP/albumin ratio (CAR) to predict steroid response. RESULTS: A total of 124 ASUC patients were admitted during a 5-year period. Median follow-up was 2.3 years. A total of 62 patients (50%) were steroid responsive, 55 patients (44%) received rescue IFX, 22 patients (18%) required colectomy within 30 days of admission, whereas a further 14 (11%) required colectomy during follow-up. By receiver operating characteristic statistics, day 3 CAR was a more accurate marker of steroid responsiveness than day 3 CRP or day 3 albumin alone [area under curve=0.75 (P<0.001)]. The optimal CAR to predict response to steroids on day 3 was 0.85 (sensitivity 70%, specificity 76%). When combined with D3 stool frequency, specificity improved to 83%. If at day 3, CAR was >0.85 and stool frequency was >3, the relative risk of steroid nonresponse was significantly raised at 3.9 (95% confidence interval, 2.1-7.2). CONCLUSIONS: Raised D3 CAR is an early predictor of steroid-refractory ASUC. When combined with D3 stool frequency, its predictive ability improves. In patients with predicted steroid nonresponse, early introduction of rescue IFX at this stage may be more effective, before serum albumin falls profoundly.

Benchmark study on glyphosate-resistant cropping systems in the United States. Part 7: Effects of weed management strategy (grower practices versus academic recommendations) on the weed soil seedbank over 6 years.

BACKGROUND: Shifts in weed species composition and richness resulting from near-exclusive reliance on herbicides in glyphosate-resistant (GR) cropping systems has necessitated the implementation of alternative weed management tactics to reduce selection pressures of herbicides. We contrasted the response of the weed soil seedbank to effects of weed management strategy, comparing grower practices with academic recommendations for best management practices (BMPs) over 6 years and across five weed hardiness zones in the US Midwest at sites subject to GR cropping systems. RESULTS: Total weed population density and species richness varied according to cropping system, location and prior year's crop, but less so to weed management strategy. The seedbank population density for 11 of the 14 most frequent weed species was affected by weed management strategy either alone or in an interaction with hardiness zone or year, or both. In only 29% of comparisons was weed population density lower following academic recommendations, and this depended upon prior crop and cropping system. The population density of high-risk weed species was reduced by academic recommendations, but only in two of six years and under continuous GR maize. Overall, the weed population density was decreasing in field halves subject to the BMPs in the academic recommendations relative to grower practices. CONCLUSION: The soil seedbank is slow to respond to academic recommendations to mitigate glyphosate-resistant weeds, but represents a biological legacy that growers need to keep in mind even when management practices reduce emerged field weed population densities.