Continuous Monitoring of CRP, IL-6, and Calprotectin in Inflammatory Bowel Disease Using a Perspiration-Based Wearable Device.

BACKGROUND: Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration. METHODS: Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed. RESULTS: A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums. CONCLUSIONS: We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

This work establishes the clinical utility of perspiration as a noninvasive, continuous marker for gut inflammation and demonstrates the ability to distinguish between active and inactive inflammatory bowel disease across perspiration, serum, and stool.

Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Lymph Node Histologic Changes.

INTRODUCTION: Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on ozanimod is unknown. MATERIALS AND METHODS: This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who received ozanimod and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens was reviewed and multiple features were scored by experienced pathologists. RESULTS: Six (13%) ozanimod-treated patients with UC required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were examined. Histologic examination of lymph nodes showed that patients treated with ozanimod had significantly greater extent of dilated sinuses (p=0.03) and greater degrees of sinus histiocytosis (p=0.03) compared with control patients. In addition, there was a trend towards more Castleman-like angiotrophic hyperplasia, plasma cell infiltration and subcortical interfollicular expansion in ozanimod treated patients. CONCLUSION: This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. The presence of sinus histiocytosis and dilated sinuses is in keeping with the known mechanism of action of ozanimod and suggests that blocking lymphocyte egression from lymph nodes was insufficient to ameliorate disease severity in these patients. The possibility of Castleman-like features identified in several of the cases, needs to be further investigated.

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience.

BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD. METHODS: We performed a prospective analysis of clinical outcomes on upadacitinib in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and fecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. RESULTS: A total of 105 patients were followed up for 8 weeks on upadacitinib, 84 of whom (44 UC patients, 40 CD patients) were initiated because of active luminal or perianal disease and included in the analysis. One hundred percent previously received anti-tumor necrosis factor therapy, and 89.3% had received 2 or more advanced therapies. At 4 and 8 weeks of treatment for UC, 19 of 25 (76.0%) and 23 of 27 (85.2%) achieved clinical response and 18 of 26 (69.2%) and 22 of 27 (81.5%) achieved clinical remission, respectively. Of those who previously were tofacitinib-exposed, 7 of 9 (77.8%) achieved clinical remission by 8 weeks. In CD, 13 of 17 (76.5.%) achieved clinical response and 12 of 17 (70.6%) achieved clinical remission by 8 weeks. Of those with increased fecal calprotectin and C-reactive protein levels, 62% and 64% normalized by week 8, respectively. Results were seen as early as week 2 in both UC and CD, with clinical remission rates of 36% and 56.3.%, respectively. Acne was the most commonly reported adverse event, occurring in 24 of 105 patients (22.9%). CONCLUSIONS: In this large real-world experience in medically resistant patients with UC or CD, we report that upadacitinib is rapidly effective and safe, including in those who had prior tofacitinib exposure. This study was approved by the Institutional Review Board at the University of Chicago (IRB20-1979).

Treat-to-target and sequencing therapies in Crohn's disease.

Crohn's disease (CD) is a chronic immune-mediated inflammatory condition which can negatively impact a patient's quality of life. The traditional management strategy for CD has focused on symptomatic control, however, this approach fails to prevent organ damage and to change the progressive course of this disease. Thus, the field has moved towards a treat-to-target strategy that includes identifying individualized objective targets, choosing a therapy based on individual factors that include disease severity and risk, closely monitoring disease activity at predefined time points, and optimizing therapies as needed. Due to the increasing number of therapies approved for CD, this review explores the various factors which should be considered in the sequencing of treatment options together with using the treat-to-target framework to control disease activity early in its course and provide holistic patient care.

Systemic Anticoagulation and Reversal.

An increasing number of patients are on anticoagulation for a variety of indications. Patients on anticoagulation who present to the hospital with life-threatening hemorrhage, whether trauma related or not, must be assessed for the reversal of anticoagulation. Identification of the type of anticoagulation, the timing of the most recent usage of anticoagulation, and the efficacy of the anticoagulation all have an impact on whether reversal agents should be used. There are a variety of reversal agents, both nonspecific and specific, that could be used for reversal; however, not all reversal agents work for all anticoagulation medication. As more anticoagulation medications are used and indications expand, providers must be aware of the reversal agents available and the efficacy and indications for these reversal agents.

Factors Associated With Fecal Calprotectin Sample Collection Compliance: An IBD Center Quality Improvement Project.

Background: Fecal calprotectin (Fcal) is a noninvasive, inexpensive biomarker of disease activity. However, patient compliance with this test is variable and incompletely described. We assessed compliance rates with Fcal tests and identified factors associated with noncompliance. Methods: A retrospective chart review of patients with inflammatory bowel disease (IBD) who had a Fcal test ordered through our center between August 2021 and December 2021 was conducted. Demographic, clinical, disease, and test-related information were recorded. Patients with incomplete Fcal orders were sent a survey to better understand their reasons for noncompliance. Simple statistical analysis and and multivariable logistic regression modeling were performed. Results: Of 303 patients, 165 (54.4%) had an order for Fcal. Of the Fcal tests ordered, 55 (33.3%) were not completed. Remission of IBD, no prior Fcal completion, and tests ordered at a distant site were all associated with test noncompletion. A multivariable logistic regression revealed that history of a prior completed Fcal test is associated with subsequent test completion (odds ratio = 2.1, 95% confidence interval 1.9-35.5, P = .004). Patients who did not complete the test described the pandemic and third-party testing center issues as the most common reasons for noncompliance. Conclusions: In this single center experience with Fcal testing in patients with IBD, we identified that a history of incomplete Fcal testing and distant location of lab testing were significantly associated with noncompletion of the test. We provide practical guidance for future utilization and compliance, including the impact of home-based testing.

Formatively assessing prospective teachers' skills in leading mathematics discussions.

Mathematics discussions are important for helping students to develop conceptual understanding and to learn disciplinary norms and practices. In recent years, there has been increased attention to teaching prospective teachers to lead discussions with students. This paper examines the possibilities of designing a formative assessment that gathers information about prospective elementary teachers' skills with leading problem-based mathematics discussions and makes sense of such information. A decomposition of the practice of leading discussions was developed and used to design the assessment. Nine first-year teachers who graduated from a range of different teacher education programs participated in the study. The findings reveal that our formative assessment works to gather information about teachers' capabilities with leading discussions and that the associated tools support making sense of the information gathered. This suggests that such tools could be useful to support the formative assessment of the developing capabilities of prospective teachers.

Thromboelastography and rotational thromboelastometry in bleeding patients with coagulopathy: Practice management guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Assessment of the immediate need for specific blood product transfusions in acutely bleeding patients is challenging. Clinical assessment and commonly used coagulation tests are inaccurate and time-consuming. The goal of this practice management guideline was to evaluate the role of the viscoelasticity tests, which are thromboelastography (TEG) and rotational thromboelastometry (ROTEM), in the management of acutely bleeding trauma, surgical, and critically ill patients. METHODS: Systematic review and meta-analyses of manuscripts comparing TEG/ROTEM with non-TEG/ROTEM-guided blood products transfusions strategies were performed. The Grading of Recommendations Assessment, Development and Evaluation methodology was applied to assess the level of evidence and create recommendations for TEG/ROTEM-guided blood product transfusions in adult trauma, surgical, and critically ill patients. RESULTS: Using TEG/ROTEM-guided blood transfusions in acutely bleeding trauma, surgical, and critically ill patients was associated with a tendency to fewer blood product transfusions in all populations. Thromboelastography/ROTEM-guided transfusions were associated with a reduced number of additional invasive hemostatic interventions (angioembolic, endoscopic, or surgical) in surgical patients. Thromboelastography/ROTEM-guided transfusions were associated with a reduction in mortality in trauma patients. CONCLUSION: In patients with ongoing hemorrhage and concern for coagulopathy, we conditionally recommend using TEG/ROTEM-guided transfusions, compared with traditional coagulation parameters, to guide blood component transfusions in each of the following three groups: adult trauma patients, adult surgical patients, and adult patients with critical illness. LEVEL OF EVIDENCE: Systematic Review/Meta-Analysis, level III.

Aggressive Soft Tissue Infections.

Necrotizing soft tissue infections (NSTI) are characterized by rapidly progressive infection that causes tissue necrosis with associated sepsis and multisystem organ failure. A rapid diagnosis is essential to decreasing the morbidity and mortality of NSTIs. There must be a high index of suspicion based on history and physical examination. There are no adjunct laboratory values or imaging that have high sensitivity and specificity in the diagnosis of NSTI. The treatment involves emergent, radical surgical debridement of involved tissues and broad spectrum antibiotics. Follow-up should include close monitoring of the wound and repeat debridements in the operating room.

Adapting an HIV prevention intervention for high-risk, incarcerated adolescents.

This study examined the effectiveness of an adapted 4-session HIV prevention program. Participants included 490 adolescents who participated in either the 8- or the adapted 4-session HIVEd program. Analyses to identify mean changes in HIV-related knowledge, attitudes, self-efficacy, and behavioral intentions between participants in either the 4- (n = 274) or 8-session (n = 216) programs were completed. Findings indicate participants in both programs had positive changes at post interview across all study outcomes. No significant differences in changes between participants in the 4- and 8-session programs were found except that male adolescents in the 4-session program had significantly higher mean changes in condom knowledge (p < .01). The adaptation of the 8-session HIVEd program was undertaken to better reach and accommodate the needs of a high risk incarcerated adolescent population. Findings demonstrate that HIV prevention interventions for high risk populations may be successfully adapted and condensed when based on rigorously evaluated and theoretically driven programs.