Citations

ABSTRACT Background Patients with erosive oesophagitis, and those with persistent symptomatic non‐erosive gastro‐oesophageal reflux disease, require long‐term maintenance treatment with acid‐suppressing agents. Aim To evaluate the safety of vonoprazan, a potassium‐competitive acid blocker, in an integrated analysis of data from clinical trials in adults. Methods We included 14 clinical trials of vonoprazan conducted in multiple countries. Mean duration of exposure in person‐years to vonoprazan ( n = 5318) was 2068, to comparators lansoprazole ( n = 1925) or esomeprazole ( n = 86) was 751, and to placebo ( n = 779) was 59. We report adverse events, serum gastrin, and liver enzyme levels as the main outcomes. Post‐marketing safety data from December 26, 2014 (date of commercialisation in Japan) to December 25, 2023, are also provided. Results Nasopharyngitis was the only adverse event reported by at least 5.0% of patients (6.94% vonoprazan, 5.07% proton pump inhibitor (PPI), 4.49% placebo). Incidence rates per 100 person‐years for serious adverse events were 10.39 for vonoprazan, 10.65 for PPIs, and 1.69 for placebo. One patient each on vonoprazan and lansoprazole was diagnosed with gastric cancer. Mean serum gastrin levels were higher on vonoprazan than lansoprazole but normalised by 4 weeks after discontinuation. Elevated liver enzyme levels were infrequent and of low magnitude with no differences between vonoprazan and PPIs. There were four deaths; none was considered related to study drug. Conclusions Vonoprazan was well tolerated. Its safety profile from both clinical trial and post‐marketing data were consistent and comparable to that of its PPI comparators with respect to treatment‐emergent adverse events.

Abstract We investigated the extent of access to Meckel's cave (MC) and the middle cranial fossa (MCF) protecting the internal carotid artery (ICA) using the retrosigmoid approach with endoscopic-assisted reverse anterior petrosectomy (EA-RAP). Five specimens were dissected using the limited and extended EA-RAP. Based on the bone removal of the internal acoustic meatus (IAM) and subarcuate fossa, exposure of the MC and ICA were statistically compared. The limited and extended EA-RAP allowed access to the medial and anterior MC (4 mm posterior to the first genu of the cavernous ICA, and 20 mm posterior to foramen rotundum [FR]). The access to the lateral MC varied with distance of 12 and 8 mm medial to the foramen ovale for the limited and extended EA-RAP, respectively. In the extended EA-RAP, the exposure of the ICA was gained by drilling with the 0-degree endoscope (3 mm) versus 45-degree endoscope (9 mm). The working distances from the midpoint of the IAM to the most medial point of the exposed ICA was 24 mm. The most lateral point of the exposed ICA varied between 0- and 45-degree endoscopes with a distance of 21 and 13 mm, respectively. A coronal plane from the posterior genu of the cavernous ICA and a sagittal plane to the common crus of the semicircular canals can define the area of MCF accessed by the EA-RAP. Drilling of the temporal bone should be carefully customized according to the patient and can be aided by endoscopic assistance for direct visualization to minimize the risk of injuries to ICA.

Objective To compare the utility of intraoperative electrically evoked auditory brainstem response (eABR) and electrically evoked stapedial reflex testing (eSRT) for cochlear nerve integrity monitoring during simultaneous translabyrinthine resection of vestibular schwannoma (VS) and cochlear implantation. Study design Historical cohort study. Setting Tertiary academic referral center. Patients Eleven patients (12 cases) who underwent translabyrinthine tumor resection with simultaneous placement of a standard, unmodified cochlear implant (CI). Intervention A CI placed at the beginning of the operation before tumor resection to facilitate intraoperative cochlear nerve monitoring through a CI-delivered electrical stimulus. Main outcome measure Correlation of intraoperative monitoring outcomes with postoperative CI performance. Results Among the 12 cases (median age, 47 years), eABR waveforms were present at the conclusion of tumor resection in 10, including 6 that achieved open set speech perception. Of the 2 cases with negative eABR, 1 achieved open set speech perception. By contrast, of the 8 cases with a positive eSRT response, 7 achieved open set speech perception. Of the 4 cases with a negative eSRT response, none achieved open set speech perception. The 3 cases that did not receive auditory stimulation included 2 with positive and 1 with negative eABR; all 3 had a negative eSRT response. Conclusions Intraoperative eSRT using an unmodified CI is a promising new method for monitoring the integrity of the cochlear nerve during simultaneous VS resection. eSRT response at the conclusion of tumor resection strongly correlated with CI open set speech capacity. Although still useful, eABR was less reliable at predicting postoperative hearing outcomes in this series.

Background: Traumatic carotid artery pseudoaneurysms (PSAs) represent a vascular anomaly with potential for serious complications, including stroke. Traditional treatments involve endovascular stenting, which may not be ideally suited to otherwise healthy vessels that have the potential to remodel. Given the limitations of smaller animal models in replicating human vasculature and the need for improved treatment modalities, this study introduces a novel swine model for the creation and evaluation of carotid PSAs. Methods: The PSAs were created from bovine dura and anastomosed in an end-to-side fashion to bilateral carotid arteries. The PSAs were radiologically followed up post-operatively and were harvested at 3 and 10 days for histological analysis. Results: Pseudoaneurysms were successfully created in both animals without intra-operative or immediate post-operative complications. Radiological analysis showed well-perfused PSAs with intra-aneurysmal turbulence, hemodynamically mimicking human carotid artery PSAs. There was no evidence of thrombus or arterial stenosis. Histological examinations revealed thrombus maturation and tight anastomosis of the PSA sac with the native artery. Conclusions: This PSA swine model offers a replicable, cost-effective, and easily implemented tool with the potential to advance carotid PSA management and educational efforts in vascular surgery. Clinical Impact The model presented in this methodology paper allows for a standardized PSA animal model allowing for the standardization of a clinical entity which is frequently heterogenenous in morphology. This can allow for the development of new therapies or provide a ground truth for computer modelling for further in silico study.

Background: Acute limb ischemia (ALI) requires prompt revascularization to preserve the extremity and minimize the effects of systemic reperfusion. Once ALI is recognized, delays in revascularization are generally due to system issues (e.g., transfer) and there is a need for a method of temporary extremity perfusion to reduce warm ischemic time. Lower Extremity Extracorporeal Distal Revascularization (LEEDR) is a percutaneous technique that uses a pump and circuit to deliver oxygenated blood into a pedal artery. Hypothesis: Extracorporeal perfusion can improve survival from ALI. Aims: The aim of this study is to use a swine model of prolonged hindlimb ischemia to compare survival and functional outcomes of LEEDR versus control (warm ischemia). Methods: Anesthetized female Yorkshire swine (40-60kg) underwent hindlimb ischemia using endovascular balloon occlusion and were randomized to control (n=6) or LEEDR (n=6). Controls underwent 9 hours of ischemia. LEEDR animals underwent contralateral femoral and ipsilateral posterior tibial artery cannulation followed by 8 hours of extracorporeal perfusion into the ischemic limb. Subjects were revascularized by removing the endovascular balloons, restoring extremity blood flow, and undergoing a 4-hour critical care period before extubation and observation for 48 hours. Primary outcome was survival and secondary outcomes included functional extremity scores (Tarlov Gait Score), compartment pressures (mmHg) and biochemical markers of reperfusion. Results: Survival was higher in animals undergoing LEEDR (83% vs. 0%; p=0.001), with most control animals succumbing to acute lung injury. LEEDR animals had a higher functional gait score (5.9±0.3 vs. 2.5±0.7; p<0.001) and lower compartment pressure (8±2 vs. 28±4; p=0.002) compared to controls. Biochemically, the LEEDR group had lower potassium (4.5±0.3 vs. 5.3±0.4; p=0.001) and lactate (1.2±0.5 vs. 2.0±0.7; p<0.001) measurements compared to controls during reperfusion and recovery. Conclusion: LEEDR can effectively mitigate 8 hours of extremity ischemia in a swine model, reducing mortality from reperfusion, while improving functional gait score and eliminating compartment syndrome. This percutaneous approach to ALI opens a new field of extracorporeal limb salvage, which can temporize extremity perfusion improving outcomes in patients who have traditionally had limited options due to prolonged warm ischemia.

AbstractBackgroundMotion of lung tumors during radiotherapy leads to decreased accuracy of the delivered dose distribution. This is especially true for proton radiotherapy due to the finite range of the proton beam. Methods for mitigating motion rely on knowing the position of the tumor during treatment.PurposeProton radiography uses the treatment beam, at an energy high enough to traverse the patient, to produce a radiograph. This work shows the first results of using an integrated‐mode proton radiography system to track the position of moving objects in an experimental phantom study; demonstrating the potential of using this method for measuring tumor motion.MethodsProton radiographs of an anthropomorphic lung phantom, with a motor‐driven tumor insert, were acquired approximately every 1 s, using tumor inserts of 10, 20, and 30 mm undergoing a known periodic motion. The proton radiography system used a monolithic scintillator block and digital cameras to capture the residual range of each pencil beam passing through the phantom. These ranges were then used to produce a water equivalent thickness map of the phantom. The centroid of the tumor insert in the radiographs was used to determine its position. This measured position was then compared to the known motion of the phantom to determine the accuracy.ResultsSubmillimeter accuracy on the measurement of the tumor insert was achieved when using a 30 mm tumor insert with a period of 24 s and was found to be improved for decreasing motion amplitudes with a mean absolute error (MAE) of 1.0, 0.9, and 0.7 mm for 20, 15, and 10 mm respectively. Using smaller tumor inserts reduced the accuracy with a MAE of 1.8 and 1.9 mm for a 20 and 10 mm insert respectively undergoing a periodic motion with an amplitude of 20 mm and a period of 24 s. Using a shorter period resulted in significant motion artifacts reducing the accuracy to a MAE of 2.2 mm for a 12 s period and 3.1 mm for a 6 s period for the 30 mm insert with an amplitude of 20 mm.ConclusionsThis work demonstrates that the position of a lung tumor insert in a realistic anthropomorphic phantom can be measured with high accuracy using proton radiographs. Results show that the accuracy of the position measurement is the highest for slower tumor motions due to a reduction in motion artifacts. This indicates that the primary obstacle to accurate measurement is the speed of the radiograph acquisition. Although the slower tumor motions used in this study are not clinically realistic, this work demonstrates the potential for using proton radiography for measuring tumor motion with an increased scanning speed that results in a decreased acquisition time.

PURPOSE The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND. METHODS The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341 ) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point. RESULTS In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor–positive/human epidermal growth factor receptor 2–negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery. CONCLUSION The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).