Citations

Abstract Background Cardiac troponin is the gold-standard biomarker for the evaluation of patients with suspected acute myocardial infarction (MI). Improvements in assay technology have led to high-sensitivity cardiac troponin assays that, when incorporated into accelerated diagnostic pathways, may rapidly diagnose or exclude acute MI more efficiently than conventional troponin assays. Content In this narrative review, we provide practical suggestions for implementing high-sensitivity cardiac troponin assays, review accelerated diagnostic pathways incorporating these assays, and review the impact of these assays on resource utilization and cost-effectiveness in relation to the evaluation of individuals with possible acute MI. Summary An increasing number of hospitals are transitioning to high-sensitivity cardiac troponin assays. This narrative review provides an overview of the potential benefits of this transition.

Abstract Coccidioidomycosis is an endemic fungal infection caused by the soil-dwelling Coccidioides. One prior study showed that persons with diabetes mellitus (DM) with elevated glucose at the time of coccidioidomycosis had poorer coccidioidal outcomes compared to persons without DM. We aimed to assess the association between hemoglobin A1C (A1C) and outcomes among persons with coccidioidomycosis and coexisting DM. We conducted a retrospective case-control study of patients with DM (cases) and without DM (controls) with coccidioidomycosis to assess the effect of glycemic control on outcomes in patients with DM. From January 1, 2017, to October 13, 2022, we identified 138 DM patients with coccidioidomycosis and compared them with 283 non-DM control patients with coccidioidomycosis. Compared with controls, cases were more likely to require hospitalization (OR 1.20, P < .001), have a lung cavity (OR 1.36, P < .001) and cavitary complications (OR 1.09, P = .001), require surgical management (OR 1.07, P = .016), and experience relapsed infection (OR 1.09, P = .041). Among the cases, when baseline A1C was assessed as a continuous variable, each 1-unit increase of A1C had a significant effect on coccidioidomycosis-related hospitalizations (A1C OR 1.59, P = .005) and the presence of cavities (OR 1.42, P = .01). Controlling for Charlson Comorbidity Index did not change the significance of A1C influence on outcomes of hospitalization and lung cavities. DM patients with A1C levels ≤8.0 at presentation did not have increased adverse coccidioidomycosis outcomes. In summary, glycemic control profoundly impacts the outcomes of diabetic patients with coccidioidomycosis.

Abstract Background Crohn’s disease (CD) treatment is associated with increased risks of infection and malignancies. Although the safety of certolizumab pegol (CZP) is well established, long-term data from community-based observational studies are lacking. Aim This study aimed to evaluate long-term safety outcomes of patients from the SECURE registry receiving CZP relative to other CD treatments, including corticosteroids, immunosuppressants, and biologics. The primary outcome of this observational study was the evaluation of malignancies. Methods Adult patients with CD were prospectively monitored for up to 8 years. Pre-specified data were collected for all enrolled patients. Adverse events of interest (AEoIs) were reported per 100 patient-years (PY) of exposure. Incidence rate ratios (IRRs) were calculated for AEoIs using multivariate regression analysis accounting for exposure to multiple treatments. Malignancies reported after any exposure to CZP were attributed to CZP. Post-hoc analyses were conducted to evaluate non-melanoma skin cancer (NMSC), lymphoma, and pregnancy outcomes. Results A total of 3072 patients were enrolled in the study. The risk of AEoIs was similar between patients with only CZP exposure versus comparator exposure. Among patients with any CZP exposure, there was a higher frequency of serious infections (IRR: 2.56 [95% confidence interval (CI): 2.00, 3.29]) and hypersensitivity or anaphylactic reactions (IRR: 4.11 [95% CI: 1.80, 9.38]) versus patients with comparator exposure. Malignancy rates were similar across groups; however, concomitant use of thiopurines was associated with higher odds of NMSC (odds ratio: 2.30 [95% CI: 1.09, 4.89]). Most cases of lymphoma (5/7) occurred in patients with exposure to thiopurines. Pregnancy outcomes were similar across groups. Conclusions No new safety signals were identified for CZP; the use of thiopurines was identified as a risk factor for NMSC. Trial registration NCT00844285.

Abstract Background Fecal microbiota, live-jslm (RBL; REBYOTA®), is the first single-dose, broad consortia, microbiota-based live biotherapeutic approved by the US Food and Drug Administration to prevent recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care antimicrobials. Inflammatory bowel disease (IBD) is a common risk factor for rCDI, yet patients with IBD are often excluded from prospective trials. This subgroup analysis of PUNCH CD3-OLS (NCT03931941) evaluated the safety and efficacy of RBL in participants with rCDI and IBD. Methods Participants with IBD (ulcerative colitis [UC], Crohn’s disease [CD], or unspecified) who had rCDI were included. Treatment-emergent adverse event (TEAE) data were collected for up to 6 months following RBL administration. Efficacy outcomes included treatment success at 8 weeks and sustained clinical response at 6 months. Results Overall, 793 participants were enrolled, and 697 received RBL; 74 had IBD (UC: n = 45; CD: n = 25; unspecified IBD: n = 4). TEAEs within 8 weeks of administration were reported by 45.9% and 47.5% of participants with and without IBD, respectively; most were mild or moderate gastrointestinal symptoms. Serious TEAEs within 8 weeks of administration were reported by 1.4% and 4.2% of participants with and without IBD, respectively. The treatment success rate at 8 weeks was 78.9%, and the sustained clinical response rate at 6 months was 91.1% in participants with IBD, similar to rates in participants without IBD (73.2% and 91.0%, respectively). Conclusions The results of this subgroup analysis of PUNCH CD3-OLS suggest RBL is safe and efficacious in patients with IBD.

AbstractBackgroundThe spatial resolution of new, photon counting detector (PCD) CT scanners is limited by the size of the focal spot. Smaller, brighter focal spots would melt the tungsten focal track of a conventional X‐ray source.PurposeTo propose focal spot multiplexing (FSM), an architecture to improve the power of small focal spots and thereby enable higher resolution clinical PCD CT. In FSM, the source rapidly alternates between multiple focal spot locations. The dwell time at each focal spot location is much shorter than the readout interval of the PCD, and each location is visited many times during the readout interval so that heat can be effectively distributed over a larger surface area. The PCD accumulates recorded events on the detector (prior to slip ring transmission) into multiple spatial bins, as a second dimension to conventional energy bins.MethodsWe estimated the maximum power permissible for a square, 0.2 mm focal spot assuming a maximum allowed surface temperature of 2900 K and a maximum transient temperature increase at the focal spot of 1400 K. This was performed using two separate thermal simulation codes: first, a commercial finite element method (FEM) was used to estimate bulk heating; second, a custom solver linearizing the heat equation was used to estimate track heating. FSM was simulated assuming that focal spot locations lay on parallel focal tracks, that instantaneous switching between tracks was possible, and that the space charge limit was never reached. We assumed a focal track velocity of 100 m/s and a 1 mm tungsten focal track layer with TZM alloy backing. The tube power was constant over a 4 s acquisition period.ResultsWithout FSM, the 0.2 mm focal spot could attain a maximum power output of 17 kW before reaching the thermal limit. FSM required a minimum switching frequency of 0.5 MHz to produce benefit. With two focal tracks and a switching frequency of 4 MHz, the power could be increased to 28 kW, and with eight focal tracks and a switching frequency of 16 MHz, the power could be increased to 98 kW. In all cases, the 1400 K transient increase thermal limit was reached before the 2900 K maximum surface temperature constraint. The relationship between maximum power, switching frequency, and number of focal tracks is discussed in relation to the underlying physics of heat transport.ConclusionsFocal spot multiplexing is an architecture that exploits the digital nature of photon counting to improve the power of high‐resolution CT X‐ray sources. With fast switching and several parallel focal tracks, it may be possible to halve the size of the focal spot while maintaining source power. This work motivates the development of new source technologies that can achieve fast electronic switching.

Abstract Background We previously identified circulating and MRI biomarkers associated with the surgical management of Crohn’s disease (CD). Here we tested associations between these biomarkers and ileal resection inflammation and collagen content. Methods Fifty CD patients undergoing ileal resection were prospectively enrolled at 4 centers. Circulating CD64, extracellular matrix protein 1 (ECM1), GM-CSF autoantibodies (GM-CSF Ab), and fecal calprotectin were measured by ELISA. Ileal 3-dimensional magnetization transfer ratio (3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, diffusion-weighted intravoxel incoherent motion (IVIM), and the simplified magnetic resonance index of activity (sMaRIA) were measured by MRI. Ileal resection specimen acute inflammation was graded, and collagen content was measured quantitatively using second harmonic imaging microscopy. Associations between biomarkers and ileal collagen content were tested. Results Median (interquartile range [IQR]) age was 19.5 (16-33) years. We observed an inverse relationship between ileal acute inflammation and collagen content (r = −0.39 [95% confidence interval {CI}: −0.61, −0.10], P = .008). Most patients (33 [66%]) received biologics, with no variation in collagen content with treatment exposures. In the univariate analysis, CD64, GM-CSF Ab, fecal calprotectin, and sMaRIA were positively associated with acute inflammation and negatively associated with collagen content (P < .1). The multivariable model for ileal collagen content (R2 = 0.31 [95% CI: 0.11, 0.52]) included log CD64 (β = −.27; P = .19), log ECM1 (β = .47; P = .06), log GM-CSF Ab (β = −.15; P = .01), IVIM f (β = .29, P = .10), and IVIM D* (β = 1.69, P = .13). Conclusions Clinically available and exploratory circulating and MRI biomarkers are associated with the degree of inflammation versus fibrosis in CD ileal resections. With further validation, these biomarkers may be used to guide medical and surgical decision-making for refractory CD.