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Introduction: Proximal duodenal electrical stimulation with various energy parameters has been investigated as a possible treatment for various gastrointestinal (GI) myoelectrical diseases. Wide pulse width (millisecond) stimulation in the proximal duodenum can disrupt or entrain the normal myoelectrical rhythm and provide a potential feedback pathway to alter normal gastric function such as emptying, fundus tone, and intra-gastric pressure and subsequently produce specific symptoms that could affect eating behaviors. A specific level of electrical stimulation is necessary to elicit symptoms and serve as an indicator that energy parameters are adequate. However, there has been no published data correlating electrical threshold stimulation with symptom characterization. The goal of this study was to determine the average minimum pulse width necessary to elicit GI symptoms. Methods: Eight patients underwent endoscopic placement of intraluminal electrodes in the proximal duodenum. Each patient received electrical stimulation in the millisecond (ms) range starting with a pulse width of 100 ms that was increased by intervals of 100 ms up to a maximum pulse width of 500 ms. The pulse repetition frequency was fixed at 12 CPM and each regimen was repeated for amplitudes ranging from 2 milliamps (mA) to 10 mA. Gastrointestinal symptom scores consisting of nausea, vomiting, satiety, fullness, pain, bloating and other, were taken at baseline and after each regimen change. Results: There was an average minimum threshold necessary for elicitation of symptoms (293.7 41.7 ms, p-value = 0.063). The three most frequently reported GI symptoms were crampy abdominal pain, fullness, and bloating. Conclusions: Electrical stimulation of the duodenum is feasible. A certain minimum threshold of duodenal electrical stimulation is necessary to elicit GI symptoms in patients. The intensity and patient tolerability of each specific GI symptom was able to be adjusted by changing a certain energy parameter within a regimen. Further research is warranted to evaluate the ability of duodenal electrical stimulation to produce GI symptoms that may alter eating behaviors. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 remains a significant risk for the immunocompromised given their lower responsiveness to vaccination or infection. Therefore, passive immunity through long-acting monoclonal antibodies (mAbs) offers a needed approach for pre-exposure prophylaxis (PrEP). Our study evaluated safety, anti-SARS-CoV-2 neutralizing activity, nasal penetration, and pharmacokinetics (PK) of two half-life-extended investigational mAbs, AER001 and AER002, providing the first demonstration of upper airway penetration of mAbs with the LS-modification., Methods: This randomized, double-blind, placebo-controlled phase I study enrolled healthy adults (n = 80) who received two long-acting COVID mAbs (AER001 and AER002), AER002 alone, or placebo. The dose ranged from 100 mg (mg) to 1200 mg per mAb component. The primary objective was to describe the safety and tolerability following intravenous (IV) administration. Secondary objectives were to describe PK, anti-drug antibodies (ADA), neutralization activity levels, and safety evaluation through 6 months of follow-up., Results: The majority (97.6%) of the reported adverse events (AE) post administration were of grade 1 severity. There were no serious adverse events (SAE) or ADAs. AER001 and AER002 successfully achieved an extended half-life of 105 days and 97.5 days, respectively. Participants receiving AER001 and AER002 (300 mg each) or AER002 (300 mg) alone showed 15- and 26-fold higher neutralization levels against D614G and omicron BA.1 than the placebo group 24 h post-administration. Single 300 or 1200 mg IV dose of AER001 and AER002 resulted in nasal mucosa transudation of approximately 2.5% and 2.7%, respectively., Conclusion: AER001 and AER002 showed an acceptable safety profile and extended half-life. High serum neutralization activity was observed against D614G and Omicron BA.1 compared to the placebo group. These data support that LS-modified mAbs can achieve durability, safety, potency, and upper airway tissue penetration and will guide the development of the next generation of mAbs for COVID-19 prevention and treatment., Trial Registration: EudraCT Number 2022-001709-35 (COV-2022-001)., (© 2024. The Author(s).)

Background: Endoscopic gastric balloons have been used effectively as weight loss devices for decades, but the requirement for endoscopy and sedation poses several limitations. The goal of this pilot study was to evaluate the safety and performance of a prototype version of Elipse™, a procedureless gastric balloon., Methods: Eight patients (mean BMI = 31.0 kg/m(2)) participated in this study. Each patient swallowed one Elipse™ balloon intended to remain in the stomach for 6 weeks, self-empty, and then pass. Each balloon was filled with 450 mL of filling fluid. Patients returned every 2 weeks for abdominal ultrasound. No specific diet or exercise plan was prescribed., Results: All eight patients successfully swallowed the device. The most common adverse events were nausea and vomiting. There were no serious adverse events, and all balloons were excreted safely. Despite not being prescribed a diet or exercise plan, all eight patients lost weight. In 6/8 patients, the balloon remained full through 6 weeks, self-emptied, and passed. In one patient, the balloon appeared partially collapsed on ultrasound after 11 days and was endoscopically punctured. One asymptomatic patient elected to have the balloon endoscopically punctured after 19 days. Both balloons passed in the stool after 4 days. In both cases, endoscopic examination of the upper GI tract showed no abnormalities., Conclusions: This pilot study demonstrates the safety and performance of Elipse™, a procedureless gastric balloon for weight loss. Future studies will test a commercial design filled to 550 mL intended to last in the stomach for at least 12 weeks.

Objective: To assess the efficacy and safety of a new surgical device designed to prevent adhesions., Design: Prospective, controlled two-phase porcine study., Setting: Good Laboratory Practice-certified animal facility., Animal(s): Phase I: 10 pigs underwent peritoneal treatment with the PROACT System (NTERO Surgical, Inc., Palo Alto, California) at the time of the laparotomy incision, and four had the incision made without treatment. Phase II: 22 animals were randomized to treatment or control groups., Intervention(s): Animals in both groups underwent laparotomy incision and small bowel resection. The treatment group received treatment to the peritoneum before the peritoneal incision was made. Necropsy and adhesion evaluation were conducted by a blinded reviewer 7-13 days after the initial surgery., Main Outcome Measure(s): Presence or absence of adhesions., Result(s): Phase I: no treated animal developed adhesions to the incision site; three of four control animals developed adhesions to the incision site. Phase II: 4 of 10 control animals and no treated animals developed midline abdominal wall adhesions. Distal adhesions tended to also be reduced in treated animals. No side effects or increased risks were noted., Conclusion(s): The PROACT System appears to be safe and efficacious in reducing adhesions to the laparotomy incision line in the porcine model.