Effectiveness of biomedical interventions on the chronic stage of traumatic brain injury: a systematic review of randomized controlled trials.

Traumatic brain injury (TBI), in any form and severity, can pose risks for developing chronic symptoms that can profoundly hinder patients' work/academic, social, and personal lives. In the past 3 decades, a multitude of pharmacological, stimulation, and exercise-based interventions have been proposed to ameliorate symptoms, memory impairment, mental fatigue, and/or sleep disturbances. However, most research is preliminary, thus limited influence on clinical practice. This review aims to systematically appraise the evidence derived from randomized controlled trials (RCT) regarding the effectiveness of pharmacological, stimulation, and exercise-based interventions in treating chronic symptoms due to TBI. Our search results indicate that despite the largest volume of literature, pharmacological interventions, especially using neurostimulant medications to treat physical, cognitive, and mental fatigue, as well as daytime sleepiness, have yielded inconsistent results, such that some studies found improvements in fatigue (e.g., Modafinil, Armodafinil) while others failed to yield the improvements after the intervention. Conversely, brain stimulation techniques (e.g., transcranial magnetic stimulation, blue light therapy) and exercise interventions were effective in ameliorating mental health symptoms and cognition. However, given that most RCTs are equipped with small sample sizes, more high-quality, larger-scale RCTs is needed.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥ 30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Semaglutide vs Endoscopic Sleeve Gastroplasty for Weight Loss.

Importance: Obesity is a disease with a large socioeconomic burden. Endoscopic sleeve gastroplasty (ESG) is a minimally invasive endoscopic bariatric procedure with wide global adoption. More recently, new weight-loss medications, such as glucagon-like peptide-1 receptor agonists (eg, semaglutide), have attracted increased attention due to their efficacy. However, their cost-effectiveness over an extended period compared with ESG is a critical gap that needs to be better explored for informed health care decision-making. Objective: To assess the cost-effectiveness of semaglutide compared with ESG over 5 years for individuals with class II obesity. Design, Setting, and Participants: This economic evaluation study, conducted from September 1, 2022, to May 31, 2023, used a Markov cohort model to compare ESG and semaglutide, with a no-treatment baseline strategy. The study comprised adult patients in the US health care system with class II obesity (body mass index [BMI] of 35-39.9). The base case was a 45-year-old patient with class II obesity (BMI of 37). Patients undergoing ESG were subjected to risks of perioperative mortality and adverse events with resultant costs and decrement in quality of life. Interventions: Strategies included treatment with semaglutide and ESG. Main Outcomes and Measures: Costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) with a willingness-to-pay threshold of $100 000/QALY. A 5-year time horizon with a cycle length of 1 month with a 3% discount rate was used. Probabilities, costs, and quality-of-life estimates of the model were derived from published literature. One-way, 2-way, and probabilistic sensitivity analyses were also performed. Results: The model found that ESG was more cost-effective than semaglutide over a 5-year time horizon, with an ICER of -$595 532/QALY. Endoscopic sleeve gastroplasty added 0.06 QALYs and reduced total cost by $33 583 relative to semaglutide. The results remained robust on 1-way and probabilistic sensitivity analyses. Endoscopic sleeve gastroplasty sustained greater weight loss over 5 years vs semaglutide (BMI of 31.7 vs 33.0). To achieve nondominance, the annual price of semaglutide, currently $13 618, would need to be $3591. Conclusions and Relevance: This study suggests that ESG is cost saving compared with semaglutide in the treatment of class II obesity. On price threshold analyses, a 3-fold decrease in the price of semaglutide is needed to achieve nondominance.

Expanded clinical phenotype spectrum correlates with variant function in SCN2A-related disorders.

SCN2A-related disorders secondary to altered function in the voltage-gated sodium channel NaV1.2 are rare with clinically heterogeneous expressions that include epilepsy, autism, and multiple severe to profound impairments and other conditions. To advance understanding of the clinical phenotypes and their relation to channel function, 81 patients (36, 44% female, median age 5.4 years) with 69 unique SCN2A variants were systematically phenotyped and their NaV1.2 channel function systematically assessed. Participants were recruited through the FamileSCN2A Foundation. Primary phenotype (epilepsy of neonatal-onset, N=27; infant onset, N=18; and later onset N=24; and autism without seizures, (N=12) was strongly correlated with a non-seizure severity index (p=0.002), which was based on presence of severe impairments in gross motor, fine motor, communication abilities, gastrostomy tube dependence, and diagnosis of cortical visual impairment and scoliosis. Non-seizure severity was greatest in the neonatal-onset group and least in the autism group (p=0.002). Children with the lowest severity indices were still severely impaired, as reflected by an average Vineland adaptive behavior composite score of 49.5 (>3 SD below the test's norm-referenced mean). Epileptic spasms were significantly more common in infant onset (67%) than in neonatal (22%) or later-onset (29%) epilepsy (p=0.007). Primary phenotype also strongly correlated with variant function (p<0.0001); gain of function and mixed function variants predominated in neonatal-onset epilepsy, shifting to moderate loss of function in infant-onset epilepsy, and severe and complete loss of function in later-onset epilepsy and autism groups. Exploratory cluster analysis identified five groups representing (1) primarily later-onset epilepsy with moderate loss of function variants and low severity indices, (2) mostly infant-onset epilepsy with moderate loss of function variants but higher severity indices, (3) late-onset and autism only with the lowest severity indices (mostly 0) and severe/complete loss of function variants. Two exclusively neonatal clusters were distinguished from each other largely on non-seizure severity scores and secondarily on variant function. The relation between primary phenotype and variant function emphasizes the role of developmental factors in the differential clinical expression of SCN2A variants based on their effects on NaV1.2 channel function. The non-seizure severity of SCN2A disorders depends on a combination of the age at seizure onset (primary phenotype) and variant function. As precision therapies for SCN2A-related disorders advance toward clinical trials, knowledge of the relationship between variant function and clinical disease expression will be valuable for identifying appropriate patients for these trials and in selecting efficient clinical outcomes.

Transoral Outlet Reduction: Expert Tips, Tricks, and Troubleshooting.

Transoral outlet reduction (TORe) is an incisionless, endoscopic procedure to address weight recurrence after Roux-en-Y gastric bypass. Given the chronic, progressive nature of obesity and the minimally invasive, anatomy preserving technique of TORe, the procedure is expected to be met with high patient acceptance and widening clinical adoption. Nevertheless, the approach to TORe has been heterogeneous. As endoscopic bariatric therapies are increasingly incorporated into the multidisciplinary management of obesity, it is crucial to have a standardized, evidence-based framework for their implementation. Here, based on the available literature and the authors' combined experience of over 1,000 TORe procedures, we present our approach to patient selection, procedural technique, troubleshooting, and patient aftercare unique to TORe.

Functional mechanism study of the allelochemical myrigalone A identifies a group of ultrapotent inhibitors of ethylene biosynthesis in plants.

Allelochemicals represent a class of natural products released by plants as root, leaf, and fruit exudates that interfere with the growth and survival of neighboring plants. Understanding how allelochemicals function to regulate plant responses may provide valuable new approaches to better control plant function. One such allelochemical, Myrigalone A (MyA) produced by Myrica gale, inhibits seed germination and seedling growth through an unknown mechanism. Here, we investigate MyA using the tractable model Dictyostelium discoideum and reveal that its activity depends on the conserved homolog of the plant ethylene synthesis protein 1-aminocyclopropane-1-carboxylic acid oxidase (ACO). Furthermore, in silico modeling predicts the direct binding of MyA to ACO within the catalytic pocket. In D. discoideum, ablation of ACO mimics the MyA-dependent developmental delay, which is partially restored by exogenous ethylene, and MyA reduces ethylene production. In Arabidopsis thaliana, MyA treatment delays seed germination, and this effect is rescued by exogenous ethylene. It also mimics the effect of established ACO inhibitors on root and hypocotyl extension, blocks ethylene-dependent root hair production, and reduces ethylene production. Finally, in silico binding analyses identify a range of highly potent ethylene inhibitors that block ethylene-dependent response and reduce ethylene production in Arabidopsis. Thus, we demonstrate a molecular mechanism by which the allelochemical MyA reduces ethylene biosynthesis and identify a range of ultrapotent inhibitors of ethylene-regulated responses.

Endoscopic Ultrasound Guided Liver Palpation As a Screening Tool for Advanced Fibrosis and Cirrhosis in Patients with Suspected Metabolic Dysfunction-Associated Steatotic Liver Disease: A Pilot Study.

BACKGROUND AND AIMS: Endoscopic liver "palpation" can be performed by indenting the liver surface under endoscopic ultrasound (EUS). Indentation depth is measured with sonographic calipers. We hypothesize that fibrotic livers are more difficult to indent, and indentation can accurately predict liver fibrosis staging. We compared EUS-guided liver palpation to conventional screening modalities in patients with suspected metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: This was a cross-sectional pilot study. Consecutive patients at three hospitals between 2021-2023 underwent EUS-guided palpation with liver biopsy. Liver palpation was compared to Fibrosis-4 index (FIB-4), AST to Platelet Ratio Index (APRI), NAFLD Fibrosis Score (NFS), and transient elastography in predicting fibrosis staging on histology. Area under the receiver operator characteristic (AUROC) curve analysis was performed. RESULTS: 73 patients were included. Mean age was 49.1 and 71.2% were female. Mean body mass index was 41.1. Indentation depth was negatively correlated with fibrosis stage (Kruskal-Willis test, p<0.0001). EUS palpation demonstrated c-statistic of 0.79 and 0.95 discriminating advanced fibrosis and cirrhosis respectively. EUS-liver palpation was superior to NFS in predicting advanced fibrosis (p=0.0057) and superior to APRI and NFS predicting cirrhosis (p=0.0099 and 0.045 respectively). EUS palpation was not significantly different versus FIB-4. EUS palpation was superior to transient elastography in predicting cirrhosis (p=0.045). Using optimal cut-offs, indentation measurement ≤3.5mm yielded 100% predictive value ruling in advanced fibrosis, and ≥4.0mm yielded 100% predictive value ruling out cirrhosis. CONCLUSIONS: EUS liver palpation is a novel, accurate, and easy-to-use screening tool for advanced fibrosis and cirrhosis in patients with MASLD.

Altered neurological and neurobehavioral phenotypes in a mouse model of the recurrent KCNB1-p.R306C voltage-sensor variant.

Pathogenic variants in KCNB1 are associated with a neurodevelopmental disorder spectrum that includes global developmental delays, cognitive impairment, abnormal electroencephalogram (EEG) patterns, and epilepsy with variable age of onset and severity. Additionally, there are prominent behavioral disturbances, including hyperactivity, aggression, and features of autism spectrum disorder. The most frequently identified recurrent variant is KCNB1-p.R306C, a missense variant located within the S4 voltage-sensing transmembrane domain. Individuals with the R306C variant exhibit mild to severe developmental delays, behavioral disorders, and a diverse spectrum of seizures. Previous in vitro characterization of R306C described altered sensitivity and cooperativity of the voltage sensor and impaired capacity for repetitive firing of neurons. Existing Kcnb1 mouse models include dominant negative missense variants, as well as knockout and frameshifts alleles. While all models recapitulate key features of KCNB1 encephalopathy, mice with dominant negative alleles were more severely affected. In contrast to existing loss-of-function and dominant-negative variants, KCNB1-p.R306C does not affect channel expression, but rather affects voltage-sensing. Thus, modeling R306C in mice provides a novel opportunity to explore impacts of a voltage-sensing mutation in Kcnb1. Using CRISPR/Cas9 genome editing, we generated the Kcnb1R306C mouse model and characterized the molecular and phenotypic effects. Consistent with the in vitro studies, neurons from Kcnb1R306C mice showed altered excitability. Heterozygous and homozygous R306C mice exhibited hyperactivity, altered susceptibility to chemoconvulsant-induced seizures, and frequent, long runs of slow spike wave discharges on EEG, reminiscent of the slow spike and wave activity characteristic of Lennox Gastaut syndrome. This novel model of channel dysfunction in Kcnb1 provides an additional, valuable tool to study KCNB1 encephalopathies. Furthermore, this allelic series of Kcnb1 mouse models will provide a unique platform to evaluate targeted therapies.

Multi-centre evaluation of variation in cumulative dose assessment in reirradiation scenarios.

BACKGROUND AND PURPOSE: Safe reirradiation relies on assessment of cumulative doses to organs at risk (OARs) across multiple treatments. Different clinical pathways can result in inconsistent estimates. Here, we quantified the consistency of cumulative dose to OARs across multi-centre clinical pathways. MATERIAL AND METHODS: We provided DICOM planning CT, structures and doses for two reirradiation cases: head & neck (HN) and lung. Participants followed their standard pathway to assess the cumulative physical and EQD2 doses (with provided α/ß values), and submitted DVH metrics and a description of their pathways. Participants could also submit physical dose distributions from Course 1 mapped onto the CT of Course 2 using their best available tools. To assess isolated impact of image registrations, a single observer accumulated each submitted spatially mapped physical dose for every participating centre. RESULTS: Cumulative dose assessment was performed by 24 participants. Pathways included rigid (n = 15), or deformable (n = 5) image registration-based 3D dose summation, visual inspection of isodose line contours (n = 1), or summation of dose metrics extracted from each course (n = 3). Largest variations were observed in near-maximum cumulative doses (25.4 - 41.8 Gy for HN, 2.4 - 33.8 Gy for lung OARs), with lower variations in volume/dose metrics to large organs. A standardised process involving spatial mapping of the first course dose to the second course CT followed by summation improved consistency for most near-maximum dose metrics in both cases. CONCLUSION: Large variations highlight the uncertainty in reporting cumulative doses in reirradiation scenarios, with implications for outcome analysis and understanding of published doses. Using a standardised workflow potentially including spatially mapped doses improves consistency in determination of accumulated dose in reirradiation scenarios.

Combination Therapy of Endoscopic Gastric Remodeling with GLP-1RA for the Treatment of MASLD.

PURPOSE: The mainstay of treatment for metabolic dysfunction-associated steatotic liver disease (MASLD) is weight loss. Endoscopic gastric remodeling (EGR) and glucagon-like peptide-1 receptor agonist (GLP-1RA) are effective weight loss therapies. This study aims to assess the effect of combining EGR with GLP-1RA on liver-related outcomes and weight profile. MATERIALS AND METHODS: This is a retrospective study of a prospectively collected registry of patients with MASLD and compensated advanced chronic liver disease (cACLD) who underwent EGR. Patients were categorized as (1) monotherapy: EGR alone and (2) combination therapy: GLP-1RA prescribed within 6 months prior to or after EGR. Outcomes included changes in noninvasive tests of hepatic fibrosis, weight profile, and insulin resistance status at 12 months. RESULTS: Thirty patients (body mass index 40.7 ± 9.3 kg/m2) were included. Of these, 12 patients (40%) underwent EGR monotherapy, and 18 patients (60%) underwent EGR + GLP-1RA combination therapy. Combination therapy group experienced greater improvements in fibrosis compared to monotherapy group (alanine aminotransferase: reduction by 55 ± 23% vs 29 ± 22% (p = 0.008), NAFLD fibrosis score: reduction by 181 ± 182% vs 30 ± 83% (p = 0.04), liver stiffness measurement on transient elastography: reduction by 54 ± 12% vs 14 ± 45% (p = 0.05)). There were greater reductions in hemoglobin A1c and homeostatic model assessment for insulin resistance in combination therapy compared to monotherapy (p < 0.05). At 12 months, the combination therapy group experienced 18.2 ± 6.6% TWL, while monotherapy group experienced 9.6 ± 3.3% TWL (p = 0.004). CONCLUSIONS: In patients with MASLD and cACLD, combination of EGR with GLP-1RA is associated with greater improvements in hepatic fibrosis, weight profile, and insulin resistance compared to EGR alone.

Outcomes and Management of Re-Establishing Bariatric Patients.

BACKGROUND: Lifelong follow-up after metabolic/bariatric surgery (MBS) is necessary to monitor for patient outcomes and nutritional status. However, many patients do not routinely follow up with their MBS team. We studied what prompted MBS patients to seek bariatric care after being lost to follow-up and the subsequent treatments they received. STUDY DESIGN: A retrospective cohort study of patients after MBS who had discontinued regular MBS follow-up but represented to the MBS clinic between July 2018 and December 2022 to re-establish care. Patients with a history of a Sleeve Gastrectomy (SG), Roux-En-Y Gastric Bypass (RYGB), and Adjustable Gastric Banding (AGB) were included. RESULTS: We identified 400 patients (83.5% female, mean age 50.3 ± 12.2 years at the time of RBC), of whom 177 (44.3%) had RYGB, 154 (38.5%) had SG, and 69 (17.2%) had AGB. Overall, recurrent weight gain (RWG) was the most common reason for presentation for all three procedures (81.2% in SG, 62.7% in RYGB, and 65.2% in AGB; p<.001). SG patients were more likely to undergo a revision MBS compared to RYGB patients (16.9% vs. 5.8%, p<.001), while RYGB patients were more likely to undergo an endoscopic intervention than SG patients (17.5% vs. 7.8%, p<.001). The response to AOM agents, specifically GLP-1 drugs, was better in RYGB patients, than SG patients. CONCLUSIONS: This study highlights RWG as the most common reason for patients after MBS seeking to re-establish care with the MBS team. SG had a higher rate of revision MBS than RYGB, whereas endoscopic interventions were performed more frequently in the RYGB group. AOM, especially GLP-1 drugs, were more effective in RYGB patients.

Definitive Closure Using an Ovine Reinforced Tissue Matrix in Contaminated Penetrating Abdominal Trauma.

BACKGROUND Cases involving penetrating abdominal trauma may be complex and often involve damage to multiple organ systems. Synthetic, biologic, and reinforced biologic matrices/reinforced tissue matrices (RBMs/RTMs) are frequently used in hernia repair and other surgical procedures requiring reinforcement, including trauma cases that require abdominal repair. CASE REPORT The first case was a 35-year-old male patient with a stab wound (SW) to the right side of the chest and the abdomen resulting in damage to the diaphragm, epicardium, liver, and duodenum. The second case was a 22-year-old male patient who suffered multiple traumas after an automated trencher accident, including a skull fracture with exposed brain and major lacerations to the shoulder and abdomen causing a large right-flank hernia. In both cases, OviTex® (TELA Bio, Inc., Malvern, PA), a reinforced tissue matrix (RTM), was used to help obtain and maintain abdominal wall closure. We also present an institutional economic analysis using data from the author's institution with average case cost and future projections for procedure volume and product usage volume through 2021. CONCLUSIONS We report favorable outcomes in a series of patients with contaminated (CDC Wound Class III) surgical fields who underwent abdominal wall closure and reinforcement with OviTex RTM. Our work adds to the growing body of literature suggesting that reinforced biologics offer a potential alternative to biological meshes in the setting of a contaminated surgical field. Additionally, in comparison to other commonly available biologic matrices, use of OviTex RTM may be a cost-effective option to achieve abdominal wall closure even in complex cases.

Divergent responses of pelagic and benthic fish body-size structure to remoteness and protection from humans.

Animal body-size variation influences multiple processes in marine ecosystems, but habitat heterogeneity has prevented a comprehensive assessment of size across pelagic (midwater) and benthic (seabed) systems along anthropic gradients. In this work, we derive fish size indicators from 17,411 stereo baited-video deployments to test for differences between pelagic and benthic responses to remoteness from human pressures and effectiveness of marine protected areas (MPAs). From records of 823,849 individual fish, we report divergent responses between systems, with pelagic size structure more profoundly eroded near human markets than benthic size structure, signifying greater vulnerability of pelagic systems to human pressure. Effective protection of benthic size structure can be achieved through MPAs placed near markets, thereby contributing to benthic habitat restoration and the recovery of associated fishes. By contrast, recovery of the world's largest and most endangered fishes in pelagic systems requires the creation of highly protected areas in remote locations, including on the High Seas, where protection efforts lag.

Isolated left sternocleidomastoid pyomyositis: a rare presentation of cervical sepsis.

An elderly gentleman self-presented to A+E with a 7-day history of significant and progressive left-sided neck pain, swelling and fevers, despite oral antibiotics from his general practitioner. Examination revealed a large left-sided neck mass involving levels 2-5 of the neck that was firm to palpate, with erythematous overlying skin.An urgent CT scan demonstrated a large collection throughout the length of the left sternocleidomastoid muscle (SCM), measuring 13×5.5×4 cm, with extensive adjacent inflammatory change. He was subsequently taken to theatre for washout and debridement, during which the collection was found to be loculated and isolated to the SCM, with surrounding structures spared.Postoperatively, he was managed with intravenous fluids and a total of 2 weeks of intravenous antibiotics. The wound partially dehisced during healing and the cavity was packed with flaminal and regularly dressed with input from the tissue viability team. This was then left to heal by secondary intention and the patient was followed up in clinic over the following weeks to ensure resolution.

Obesity Is Associated with Altered Rectal Sensitivity in Chronic Constipation.

BACKGROUND: Defecation dysfunction may contribute to chronic constipation (CC), but the impact of obesity on anorectal physiology in CC remains unclear. We aimed to evaluate the relationship between obesity and anorectal function on physiologic testing in patients presenting with CC. METHODS: This was a retrospective cohort study of consecutive adults who underwent high resolution anorectal manometry (HRAM) at a tertiary center for CC. Patient demographics, clinical history, surgical/obstetric history, medications, and HRAM results were reviewed. Patients were classified into obese (BMI > 30 kg/m2) vs non-obese (BMI < 30 kg/m2) groups at the time of HRAM. Fisher-exact/student t-test for univariate analyses and general linear regression for multivariable analysis were performed. RESULTS: 383 adults (mean 50.3 years; 85.8% female) with CC were included. On HRAM, patients with obesity had lower anal sphincter resting tone (37.3 vs 48.5 mmHg, p = 0.005) and maximum squeeze pressure (104.8 mmHg vs 120.0 mmHg, p = 0.043). No significant differences in dyssynergia (61% vs 53%, p = 0.294) and failed balloon expulsion (18% vs 25%, p = 0.381) were found between obese and non-obese groups. On balloon distention testing, the maximum tolerated (163.5 vs 147.6 mL, p = 0.042) and urge sensation (113.9 vs 103.7 mL, p = 0.048) volumes were significantly increased among patients with obesity. After adjusting for potential confounders, obesity remained independently associated with increased maximum tolerated volume (ß-coefficient 13.7, p = 0.049). CONCLUSION: Obesity was independently associated with altered rectal sensitivity among patients with CC. Altered rectal sensation may play an important role in CC among patients with obesity. Anorectal physiology testing should be considered to understand the pathophysiology and guide management.

Novel upper gastrointestinal bleeding sensor capsule: a first human feasibility and safety trial.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is the most common GI condition requiring hospitalization, and can be diagnosed by direct visualization. The present study aimed to evaluate the safety and feasibility of using the PillSense system (EnteraSense Ltd.), a novel diagnostic tool designed for the rapid in vivo detection of UGIB, in human volunteers. METHODS: In the present study, 10 volunteers swallowed a PillSense capsule, followed by 2 servings of an autologous blood preparation. Participants were monitored for capsule passage, overall tolerability of the procedure, and adverse events. RESULTS: The procedure was completed per the protocol established in the present study in 9/10 cases. In 9 of the subjects, after capsule ingestion, the device indicated the absence of blood with sensor output values of 1. After the ingestion of the first blood mixture, the sensor outputs of all devices increased from 2.8 to 4, indicating that each camera detected blood. The sensor output remained within that range after the ingestion of the second mixture; however, in one case, the baseline capsule signal was positive, because of a preexisting condition. The passage of the capsule was verified in all patients, and no adverse events were reported. CONCLUSION: The first trial of the PillSense system in human subjects demonstrated the feasibility, safety, and tolerability of utilizing this product as a novel, noninvasive, and easy-to-use triage tool for the diagnosis of patients suspected of having UGIB.

Preclinical study of a novel ingestible bleeding sensor for upper gastrointestinal bleeding.

BACKGROUND/AIMS: Upper gastrointestinal bleeding (UGIB) is a life-threatening condition that necessitates early identification and intervention and is associated with substantial morbidity, mortality, and socioeconomic burden. However, several diagnostic challenges remain regarding risk stratification and the optimal timing of endoscopy. The PillSense System is a noninvasive device developed to detect blood in patients with UGIB in real time. This study aimed to assess the safety and performance characteristics of PillSense using a simulated bleeding model. METHODS: A preclinical study was performed using an in vivo porcine model (14 animals). Fourteen PillSense capsules were endoscopically placed in the stomach and blood was injected into the stomach to simulate bleeding. The safety and sensitivity of blood detection and pill excretion were also investigated. RESULTS: All the sensors successfully detected the presence or absence of blood. The minimum threshold was 9% blood concentration, with additional detection of increasing concentrations of up to 22.5% blood. All the sensors passed naturally through the gastrointestinal tract. CONCLUSION: This study demonstrated the ability of the PillSense System sensor to detect UGIB across a wide range of blood concentrations. This ingestible device detects UGIB in real time and has the potential to be an effective tool to supplement the current standard of care. These favorable results will be further investigated in future clinical studies.