Delayed CCL23 response is associated with poor outcomes after cardiac arrest.

Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest.

Community consultation for Exception from Informed consent (EFIC) before and during the COVID-19 pandemic.

Aim: Describe community consultation and surrogate consent rates for two Exception From Informed Consent (EFIC) trials for out-of-hospital cardiac arrest (OOHCA) - before and during the COVID-19 pandemic. Methods: The PEARL study (2016-2018) randomized OOHCA patients without ST-elevation to early cardiac catheterization or not. Community consultation included flyers, radio announcements, newspaper advertisements, mailings, and in-person surveys at basketball games and ED waiting rooms. The PROTECT trial (2021-present) randomizes OOHCA survivors to prophylactic ceftriaxone or placebo; the community consultation plan during the pandemic included city council presentations, social media posts, outpatient flyers, but no in-person encounters. Demographics for PROTECT community consultation were compared to PEARL and INTCAR registry data, with p-value < 0.05 considered significant. Results: PEARL surveyed 1,362 adults, including 64 % ≥60 years old, 96 % high school graduates or beyond; research acceptance rate was 92 % for the community and 76 % for personal level. PROTECT initially obtained 221 surveys from electronic media - including fewer males (28 % vs 72 %,p < 0.001) and those > 60 years old (14 % vs 53 %;p < 0.001) compared to INTCAR. These differences prompted a revised community consultation plan, targeting 79 adult in-patients with cardiac disease which better matched PEARL and INTCAR data: the majority were ≥ 60 years old (66 %) and male (54 %). Both PEARL and PROTECT enrolled more patients using surrogate consent vs EFIC (57 %, 61 %), including 71 % as remote electronic consents during PROTECT. Conclusions: Community consultation for EFIC studies changed with the COVID-19 pandemic, resulting in different demographic patterns. We describe effective adaptations to community consultation and surrogate consent during the pandemic.

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial.

BACKGROUND: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. METHODS: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. DISCUSSION: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

Impact of a ring-fitted cap on insertion time and adenoma detection: a randomized controlled trial.

BACKGROUND AND AIMS: Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring-fitted cap (EndoRings; EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. METHODS: This was a single-center, randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate, insertion times, withdrawal times, and ease of passage through the sigmoid colon. RESULTS: EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, P = .025), but there were no statistically significant differences in ADR or sessile serrated polyp detection rate. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with Endo-Rings and contributed substantially to the overall results. CONCLUSIONS: EndoRings can increase adenoma detection without a significant increase in procedure time, but the effect varies between operators. The use of EndoRings slows colonoscope insertion. (Clinical trial registration number: NCT03418662.).

Endocuff Vision Reduces Inspection Time Without Decreasing Lesion Detection: A Clinical Randomized Trial.

BACKGROUND & AIMS: Mucosal exposure devices improve detection of lesions during colonoscopy and have reduced examination times in uncontrolled studies. We performed a randomized trial of Endocuff Vision vs standard colonoscopy to compare differences in withdrawal time (the primary end point). We proposed that Endocuff Vision would allow complete mucosal inspection in a shorter time without impairing lesion detection. METHODS: Adults older than 40 years undergoing screening or surveillance colonoscopies were randomly assigned to the Endocuff group (n=101, 43.6% women) or the standard colonoscopy group (n=99; 57.6% women). One of 2 experienced endoscopists performed the colonoscopies, aiming for a thorough evaluation of the proximal sides of all haustral folds, flexures, and valves in the shortest time possible. Inspection time was measured with a stopwatch and calculated by subtracting washing, suctioning, polypectomy and biopsy times from total withdrawal time. RESULTS: There were significantly fewer women in the Endocuff arm (P = .0475) but there were no other demographic differences between groups. Mean insertion time with Endocuff was 4.0 min vs 4.4 min for standard colonoscopy (P = .14). Mean inspection time with Endocuff was 6.5 min vs 8.4 min for standard colonoscopy (P < .0001). Numbers of adenomas detected per colonoscopy (1.43 vs 1.07; P = .07), adenoma detection rate (61.4% vs 52%; P = .21), number of sessile serrated polyps per colonoscopy (0.27 vs 0.21; P = .12), and sessile serrated polyp detection rate (19.8% vs 11.1%; P = .09) were all higher with Endocuff Vision. Results did not differ significantly when we controlled for age, sex, or race. CONCLUSION: In a randomized trial, we found inclusion of Endocuff in screening or surveillance colonoscopies to decrease examination time without reducing lesion detection. ClinicalTrials.gov, Number: NCT03361917.

A comparison of 2 distal attachment mucosal exposure devices: a noninferiority randomized controlled trial.

BACKGROUND AND AIMS: Endocuff (Arc Medical Design, Leeds, UK) and Endocuff Vision (Arc Medical Design, Leeds, UK) are effective mucosal exposure devices for improving polyp detection during colonoscopy. AmplifEYE (Medivators Inc, Minneapolis, Minn, USA) is a device that appears similar to the Endocuff devices but has received minimal clinical testing. METHODS: We performed a randomized controlled clinical trial using a noninferiority design to compare Endocuff Vision with AmplifEYE. RESULTS: The primary endpoint of adenomas per colonoscopy was similar in AmplifEYE at 1.63 (standard deviation 2.83) versus 1.51 (2.29) with Endocuff Vision (P = .535). The 95% lower confidence limit was 0.88 for ratio of means, establishing noninferiority of AmplifEYE (P = .008). There was no difference between the arms for mean insertion time, and mean inspection time (withdrawal time minus polypectomy time and time for washing and suctioning) was shorter with AmplifEYE (6.8 minutes vs 6.9 minutes, P = .042). CONCLUSIONS: AmplifEYE is noninferior to Endocuff Vision for adenoma detection. The decision on which device to use can be based on cost. Additional comparisons of AmplifEYE with Endocuff by other investigators are warranted. (Clinical trial registration number: NCT03560128.).

SIC-8000 versus hetastarch as a submucosal injection fluid for EMR: a randomized controlled trial.

BACKGROUND AND AIMS: Viscous solutions provide a superior submucosal cushion for EMR. SIC-8000 (Eleview; Aries Pharmaceuticals, La Jolla, Calif) is a commercially available U.S. Food and Drug Administration-approved solution, but hetastarch is also advocated. We performed a randomized trial comparing SIC-8000 with hetastarch as submucosal injection agents for colorectal EMR. METHODS: This was a single-center, double-blinded, randomized controlled trial performed at a tertiary referral center. Patients were referred to our center with flat or sessile lesions measuring ≥15 mm in size. The primary outcome measures were the Sydney resection quotient (SRQ) and the rate of en bloc resections. Secondary outcomes were total volume needed for a sufficient lift, number of resected pieces, and adverse events. RESULTS: There were 158 patients with 159 adenomas (SIC-8000, 84; hetastarch, 75) and 57 serrated lesions (SIC-8000, 30; hetastarch, 27). SRQ was significantly better in the SIC-8000 group compared with hetastarch group (9.3 vs 8.1, P = .001). There was no difference in the proportion of lesions with en bloc resections. The total volume of injectate was significantly lower with SIC-8000 (14.8 mL vs 20.6 mL, P = .038). CONCLUSIONS: SIC-8000 is superior to hetastarch for use during EMR in terms of SRQ and total volume needed, although the absolute differences were small. (Clinical trial registration number: NCT03350217.).