Measurement and Application of Incidentally Detected Coronary Calcium: JACC Review Topic of the Week.

Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems.

Therapeutic drug monitoring in inflammatory bowel disease patients on vedolizumab.

OBJECTIVE: We aimed to investigate whether vedolizumab (VDZ) levels were associated with inflammatory markers or clinical or endoscopic scoring in inflammatory bowel disease (IBD). METHODS: Besides demographic data, clinical scoring, endoscopic data, and laboratory markers of IBD patients treated with VDZ from 2015 to 2020 who had trough levels drawn on maintenance therapy were collected at baseline and at follow-up (after at least 8 weeks on VDZ therapy or after change in dose frequency). Low drug levels were defined as VDZ trough <20 µg/mL. RESULTS: We identified 89 patients with a mean age of 42.9 years. Of the 90 total trough levels drawn, 61.1% were low. Among patients on every 8 week (Q8 week) VDZ dosing, 81.5% had low troughs. After increasing dosing frequency to Q4 weeks, all patients showed improvement in VDZ levels, but 30.6% remained <20 µg/mL. Higher VDZ levels on Q8 week dosing were associated with higher albumin levels (P = 0.01). While higher VDZ levels on Q4 week dosing were associated with higher albumin (P = 0.02), lower erythrocyte sedimentation rate (P = 0.04) and higher likelihood of having mild disease or endoscopic remission (P = 0.01). No significant association was found between VDZ levels and clinical scoring, body mass index, hemoglobin, vitamin D or platelet levels on either Q8 or Q4 week dosing. CONCLUSIONS: Higher VDZ troughs were associated with higher albumin, mild endoscopic disease or endoscopic remission. Patients who continue to have low VDZ troughs despite Q4 week dosing may require a change in therapy.

Therapeutic drug monitoring in patients with inflammatory bowel disease on ustekinumab.

OBJECTIVE: Therapeutic drug monitoring is used clinically to guide anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD), but its use for ustekinumab (UST) remains unclear. This study aimed to determine predictive variables of UST levels. METHODS: In this retrospective cohort of patients with IBD, UST trough levels were drawn at maintenance dosing. Relationships between UST trough levels and demographics, therapy, and outcomes were analyzed. Machine-learning models were used to infer combinatorial traits predictive of UST levels. RESULTS: Altogether 177 patients with IBD on UST had a mean UST trough level of 4.742 µg/mL. The injection schedule correlated significantly (P < 0.001) with UST levels. Naiveté to anti-TNFs correlated with higher UST levels (P = 0.048). Univariate analysis revealed that higher inflammatory biomarkers significantly correlated to lower UST levels and a lower Simple Endoscopic Score to Crohn's Disease to adequate UST levels (P = 0.018). Multivariate analysis identified body mass index (BMI), previous anti-TNF failure, and laboratory flare as predictors of UST levels with an area under the receiver operating characteristic curve (AUROC) of 0.72. The UST cut-off level of 5.77 µg/mL yielded a 0.79 AUROC, 80% sensitivity, and 81% specificity for predicting endoscopic remission of Crohn's disease. For the clinical remission end-point in ulcerative colitis, UST level of 4.73 µg/mL yielded a 0.69 AUROC, 53% sensitivity, and 86% specificity. CONCLUSIONS: Higher UST levels correlated with less disease activity. BMI was an important consideration for UST response as well. Therefore, UST dose adjustments to reach target levels may optimize response.

Look What the Cat Dragged in! Recurrent Clostridioides difficile from a Household Cat.

BACKGROUND Clostridioides difficile (C. difficile) is a bacterium that is well known for causing serious diarrheal infections and can even lead to colon cancer if left untreated. Disruption of the normal healthy bacteria in the colon can lead to development of C. difficile colitis. Risk factors for C. difficile infections (CDI) include recent antibiotic exposure, hospital or nursing home stays, inflammatory bowel disease (IBD), or impaired immunity. There is an increasing incidence of community-associated CDI (CA-CDI) in individuals without the common risk factors, which has implicated natural reservoirs, zoonoses, originating from animals such as domestic cats and dogs, livestock, shellfish, and wild animals. CASE REPORT A previously healthy 31-year-old woman with recurrent CA-CDI suspected to be acquired from a household cat represents a novel presentation. The patient had an initial case of severe diarrhea following recent antibiotic exposure, was briefly monitored in hospital, and was diagnosed with CDI. She was trialed on oral vancomycin, which resulted in temporary resolution of her symptoms. Her symptoms recurred, however, and did not improve despite treatment with multiple therapeutic options over a period of months. Ultimately, the patient was not able to achieve long-term resolution of her symptoms until her newly adopted pet cat was treated by a veterinarian. CONCLUSIONS In conclusion, this case report explores the epidemiologic risk factors of zoonotic CA-CDI and the importance of early identification, evaluation, and prevention of disease. This case demonstrates the significance of thorough history taking, contact (pet) tracing, and proper treatment of recurrent CA-CDI.

Integrating Intestinal Ultrasound into an Inflammatory Bowel Disease Practice: How to Get Started.

Intestinal ultrasound (IUS) offers a safe, noninvasive, point-of-care tool for diagnosing and monitoring disease activity in patients with inflammatory bowel disease (IBD). IUS is used widely in Europe and Canada for IBD, but it remains underutilized in the United States. Growing interest in IUS in the United States has prompted many IBD centers to train their faculty in IUS. This, however, raises questions about how to effectively use this new tool in the United States, which does not use a social medicine model like those implemented in Europe and Canada. Here, we provide a practical framework for incorporating IUS in an IBD practice in the United States, including training requirements, equipment, and protocols for implementing IUS in daily practice.

Association between sleep variability and time in range of glucose levels in patients with type 1 diabetes: Cross-sectional study.

OBJECTIVE: Sleep and circadian disturbances emerge as novel factors influencing glycemic control in type 1 diabetes (T1D). We aimed to explore the associations among sleep, behavioral circadian parameters, self-care, and glycemic parameters in T1D. METHODS: Seventy-six non-shift-working adult T1D patients participated. Blinded 7-day continuous glucose monitoring (CGM) and hemoglobin A1C (A1C) were collected. Percentages of time-in-range (glucose levels 70-180 mg/dL) and glycemic variability (measured by the coefficient of variation [%CV]) were calculated from CGM. Sleep (duration and efficiency) was recorded using 7-day actigraphy. Variability (standard deviation) of midsleep time was used to represent sleep variability. Nonparametric behavioral circadian variables were derived from actigraphy activity recordings. Self-care was measured by diabetes self-management questionnaire-revised. Multiple regression analyses were performed to identify independent predictors of glycemic parameters. RESULTS: Median (interquartile range) age was 34.0 (27.2, 43.1) years, 48 (63.2%) were female, and median (interquartile range) A1C was 6.8% (6.2, 7.4). Sleep duration, efficiency, and nonparametric behavioral circadian variables were not associated with glycemic parameters. After adjusting for age, sex, insulin delivery mode/CGM use, and ethnicity, each hour increase in sleep variability was associated with 9.64% less time-in-range (B = -9.64, 95% confidence interval [-16.29, -2.99], p ≤ .001). A higher diabetes self-management questionnaire score was an independent predictor of lower A1C (B = -0.18, 95% confidence interval [-0.32, -0.04]). CONCLUSION: Greater sleep timing variability is independently associated with less time spent in the desirable glucose range in this T1D cohort. Reducing sleep timing variability could potentially lead to improved metabolic control and should be explored in future research. DATA AVAILABILITY STATEMENT: Data are available upon a reasonable request to the corresponding author.

Utility of Intestinal Ultrasound in Clinical Decision-Making for Inflammatory Bowel Disease.

Background: There is a clinical need to improve the monitoring of inflammatory bowel disease (IBD) activity. Despite being used regularly in European countries, intestinal ultrasound (IUS) has been implemented less in the United States for unclear reasons. Aims: The aim of this study is to illustrate how IUS can be used as a clinical decision-making tool in an American IBD cohort. Methods: This retrospective cohort analysis evaluated patients with IBD seen at our institution who underwent IUS as part of routine evaluation of their IBD from July 2020 to March 2022. To evaluate the clinical utility of IUS for different patient populations and against more frequently used measures of inflammation, we compared patient demographics, inflammatory markers, clinical scores, and medications between patients in remission and those with active inflammation. Treatment plans between the 2 groups were compared and we analyzed patients with follow-up IUS visits to validate treatment plan decisions at initial evaluation. Results: Out of 148 total patients with IUS, we found that 62.1% (N = 92) of our patients had active disease and 37.9% (N = 56) were in remission. Ulcerative colitis activity index and Mayo scores were both significantly correlated with IUS findings. The treatment plan was significantly correlated with IUS findings (P = .004). At follow-up, we observed an overall decrease in intestinal thickening, improvements in vascular flow, and mural stratification. Conclusions: Clinical decisions incorporating IUS findings effectively reduced inflammation in our IBD patients. IUS should be strongly considered by IBD clinicians in the United States for monitoring disease activity in IBD.

The Role of Fecal Microbiota Transplantation in the Induction of Remission in Ulcerative Colitis.

BACKGROUND: Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC). SUMMARY: While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance toward optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid-producing bacteria, Clostridium clusters IV and XIVa, Odoribacter splanchnicus, and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC. KEY MESSAGES: There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.

Sleep optimization to improve glycemic control in adults with type 1 diabetes: study protocol for a randomized controlled parallel intervention trial.

BACKGROUND: Despite improvements in treatment regimens and technology, less than 20% of adults with type 1 diabetes (T1D) achieve glycemic targets. Sleep is increasingly recognized as a potentially modifiable target for improving glycemic control. Diabetes distress, poor self-management behaviors, and reduced quality of life have also been linked to sleep variability and insufficient sleep duration. A significant gap of knowledge exists regarding interventions to improve sleep and the effects of sleep optimization on glycemic control in T1D. The purpose of this study is to determine the efficacy of a T1D-specific sleep optimization intervention (Sleep-Opt) on the primary outcomes of sleep variability, sleep duration, and glycemic control (A1C); other glycemic parameters (glycemic variability, time-in-range [TIR]); diabetes distress; self-management behaviors; quality of life; and other patient-reported outcomes in adults with T1D and habitual increased sleep variability or short sleep duration. METHODS: A randomized controlled parallel-arm study will be employed in 120 adults (aged 18 to 65 years) with T1D. Participants will be screened for habitual sleep variability (> 1 h/week) or insufficient sleep duration (< 6.5 h per night). Eligible subjects will be randomized to the Sleep-Opt intervention group or healthy living attention control group for 12 weeks. A 1-week run-in period is planned, with baseline measures of sleep by actigraphy (sleep variability and duration), glycemia (A1C and related glycemic measures: glycemic variability and TIR using continuous glucose monitoring), and other secondary outcomes: diabetes distress, self-management behaviors, quality of life, and additional patient-reported outcomes. Sleep-Opt is a technology-assisted behavioral sleep intervention that we recently developed that leverages the rapidly increasing public interest in sleep tracking. Our behavioral intervention employs four elements: a wearable sleep tracker, didactic content, an interactive smartphone application, and brief telephone counseling. The attention control group will participate in a healthy living information program. Baseline measures will be repeated at midpoint, program completion, and post-program (weeks 6, 12, and 24, respectively) to determine differences between the two groups and sustainability of the intervention. DISCUSSION: A better understanding of strategies to improve sleep in persons with T1D has the potential to be an important component of diabetes. TRIAL REGISTRATION: Clinical Trial Registration: NCT04506151 .

Biological Therapies for the Management of Enteric Disease: Considerations for the Clinician.

Several biologic therapies have been approved for enteric diseases. We evaluate each biologic's role based on their mechanism of action in treating these conditions. This review examines data on efficacy and safety, as well as considerations for using these therapies in clinical practice in inflammatory bowel diseases, enteric infections-specifically Clostridioides difficile colitis-and potentially in the increasingly prevalent disorder of eosinophilic esophagitis. When choosing an appropriate therapy, it is important to assess patient severity, as most biologics are approved for those with moderate to severe disease activity. With many years of data from clinical trials and real-world experience, these therapies have been shown to improve outcomes overall in enteric diseases, contributing to more options for our patients.