Most Promising Approaches to Improve Stroke Outcomes: The Stroke Treatment Academic Industry Roundtable XII Workshop.

The Stroke Treatment Academic Industry Roundtable XII included a workshop to discuss the most promising approaches to improve outcome from acute stroke. The workshop brought together representatives from academia, industry, and government representatives. The discussion examined approaches in 4 epochs: pre-reperfusion, reperfusion, post-reperfusion, and access to acute stroke interventions. The participants identified areas of priority for developing new and existing treatments and approaches to improve stroke outcomes. Although many advances in acute stroke therapy have been achieved, more work is necessary for reperfusion therapies to benefit the most possible patients. Prioritization of promising approaches should help guide the use of resources and investigator efforts.

Priorities for Advancements in Neuroimaging in the Diagnostic Workup of Acute Stroke.

STAIR XII (12th Stroke Treatment Academy Industry Roundtable) included a workshop to discuss the priorities for advancements in neuroimaging in the diagnostic workup of acute ischemic stroke. The workshop brought together representatives from academia, industry, and government. The participants identified 10 critical areas of priority for the advancement of acute stroke imaging. These include enhancing imaging capabilities at primary and comprehensive stroke centers, refining the analysis and characterization of clots, establishing imaging criteria that can predict the response to reperfusion, optimizing the Thrombolysis in Cerebral Infarction scale, predicting first-pass reperfusion outcomes, improving imaging techniques post-reperfusion therapy, detecting early ischemia on noncontrast computed tomography, enhancing cone beam computed tomography, advancing mobile stroke units, and leveraging high-resolution vessel wall imaging to gain deeper insights into pathology. Imaging in acute ischemic stroke treatment has advanced significantly, but important challenges remain that need to be addressed. A combined effort from academic investigators, industry, and regulators is needed to improve imaging technologies and, ultimately, patient outcomes.

Enhancing Enrollment in Acute Stroke Trials: Current State and Consensus Recommendations.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community's understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration.

Performance of gene-expression profiling test score variability to predict future clinical events in heart transplant recipients.

BACKGROUND: A single non-invasive gene expression profiling (GEP) test (AlloMap®) is often used to discriminate if a heart transplant recipient is at a low risk of acute cellular rejection at time of testing. In a randomized trial, use of the test (a GEP score from 0-40) has been shown to be non-inferior to a routine endomyocardial biopsy for surveillance after heart transplantation in selected low-risk patients with respect to clinical outcomes. Recently, it was suggested that the within-patient variability of consecutive GEP scores may be used to independently predict future clinical events; however, future studies were recommended. Here we performed an analysis of an independent patient population to determine the prognostic utility of within-patient variability of GEP scores in predicting future clinical events. METHODS: We defined the GEP score variability as the standard deviation of four GEP scores collected ≥315 days post-transplantation. Of the 737 patients from the Cardiac Allograft Rejection Gene Expression Observational (CARGO) II trial, 36 were assigned to the composite event group (death, re-transplantation or graft failure ≥315 days post-transplantation and within 3 years of the final GEP test) and 55 were assigned to the control group (non-event patients). In this case-controlled study, the performance of GEP score variability to predict future events was evaluated by the area under the receiver operator characteristics curve (AUC ROC). The negative predictive values (NPV) and positive predictive values (PPV) including 95 % confidence intervals (CI) of GEP score variability were calculated. RESULTS: The estimated prevalence of events was 17 %. Events occurred at a median of 391 (inter-quartile range 376) days after the final GEP test. The GEP variability AUC ROC for the prediction of a composite event was 0.72 (95 % CI 0.6-0.8). The NPV for GEP score variability of 0.6 was 97 % (95 % CI 91.4-100.0); the PPV for GEP score variability of 1.5 was 35.4 % (95 % CI 13.5-75.8). CONCLUSION: In heart transplant recipients, a GEP score variability may be used to predict the probability that a composite event will occur within 3 years after the last GEP score. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00761787.

Long-term outcomes after transoral incisionless fundoplication in patients with GERD and LPR symptoms.

BACKGROUND: A retrospective study evaluated safety, symptom resolution, patient satisfaction, and medication use 1-2 years after transoral incisionless fundoplication (TIF) in patients with gastroesophageal reflux disease (GERD) and/or laryngopharyngeal reflux (LPR) symptoms. METHODS: Thirty-four patients with a confirmed diagnosis of GERD symptoms that were inadequately controlled by antisecretory medications, and who where either dissatisfied with their current therapy or not willing to continue taking medication, underwent TIF using EsophyX at our community-based hospital. Follow-up assessments were completed in 28 patients. RESULTS: Median age of the study group was 57 (range = 23-77) years, BMI was 25.7 (18.3-36.4) kg/m(2), and 50% were female. All patients had documented chronic GERD for a median 5 (1-20) years and refractory symptoms to proton pump inhibitors (PPIs). Hiatal hernia was present in 75% (21/28) of patients, and 21% (6/28) had erosive esophagitis (LA grade A or B). TIF was performed following a standardized TIF-2 protocol and resulted in reducing hiatal hernia and restoring the natural anatomy of the gastroesophageal (GE) junction (Hill grade I). There were no postoperative complications. At a median 14-months follow-up, 82% (23/28) of patients were off daily PPIs (64% completely off PPIs), and 68% (19/28) were satisfied with their current health condition compared to 4% before TIF. Median GERD Health-Related Quality of Life scores were significantly reduced to 4 (0-25) from 26 (0-45) before TIF (P < 0.001). Heartburn was eliminated in 65% (17/26) and improved by >50% in 86% (24/28) of patients. Regurgitation was eliminated in 80% (16/20) of patients. Atypical LPR symptoms such as hoarseness, coughing, and throat clearing were eliminated in 63% (17/27) of patients as measured by Reflux Symptom Index scores. CONCLUSION: Our results in 28 patients confirm the safety and effectiveness of TIF, documenting symptomatic improvement of GERD and LPR symptoms and clinically significant discontinuation of daily PPIs in 82% of patients.

The effects of transoral incisionless fundoplication on chronic GERD patients: 12-month prospective multicenter experience.

PURPOSE: This study aimed to assess the impact of transoral incisionless fundoplication (TIF) on patients with chronic gastroesophageal reflux disease (GERD) at 12-month follow-up. METHODS: Clinical outcomes of 100 consecutive patients with chronic GERD who underwent TIF between January 2010 and February 2011 were analyzed. RESULTS: There were no major complications reported. Esophageal acid exposure was normalized in 14/27 (52%) of patients who underwent 12-month pH testing. Seventy-four percent of all patients were off proton pump inhibitors versus 92% on daily proton pump inhibitors before TIF, P<0.001. Daily bothersome heartburn and regurgitation symptoms were eliminated in 66/85 (78%) and 48/58 (83%) of patients. Median reflux symptom index score was reduced from 20 (0 to 41) to 5 (0 to 44), P<0.001. Two patients reported de novo dysphagia and 1 patient reported bloating (scores 0 to 3). Six patients underwent revision; 5 laparoscopic Nissen fundoplication and 1 TIF. CONCLUSIONS: TIF provided a safe and effective therapeutic option for carefully selected patients with chronic GERD.

Short-term safety and symptomatic outcomes of transoral incisionless fundoplication with or without hiatal hernia repair in patients with chronic gastroesophageal reflux disease.

BACKGROUND: A retrospective community-based study evaluated the safety and symptomatic outcomes of the transoral incisionless fundoplication (TIF) procedure with or without hiatal hernia repair (HHR) in patients with chronic gastroesophageal reflux disease (GERD). MATERIALS AND METHODS: Forty-eight patients underwent TIF using EsophyX (EndoGastric Solutions, Redmond, WA) in 3 community hospitals. Patients who presented with a hiatal hernia 3 cm or more in the greatest transverse diameter underwent laparoscopic HHR before TIF. RESULTS: Forty-two patients completed follow-up assessment at a median of 6 (range 1-11) months. Laparoscopic HHR was performed in 18 (43%) patients before TIF. There were no long-term postoperative complications. GERD-health related quality of life scores indicated heartburn elimination in 63% of patients. The need for daily proton pump inhibitor (PPI) therapy was eliminated in 76% of patients. Atypical symptom relief measured by the median reflux symptom index score reduction was significant (5 [0-47] vs 22 [2-42] on PPIs, P < .001). CONCLUSIONS: Our results support the safety and symptomatic improvement of TIF with or without laparoscopic HHR. The patients' symptoms were significantly improved, and PPI use was significantly reduced.