Potential Indications Research Articles

Prokinetics-safety and efficacy: The European Society of Neurogastroenterology and Motility/The American Neurogastroenterology and Motility Society expert review.

Prokinetics are a class of pharmacological drugs designed to improve gastrointestinal (GI) motility, either regionally or across the whole gut. Each drug has its merits and drawbacks, and based on current evidence as high-quality studies are limited, we have no clear recommendation on one class or other. However, there remains a large unmet need for both regionally selective and/or globally acting prokinetic drugs that work primarily intraluminally and are safe and without systemic side effects. Here, we describe the strengths and weaknesses of six classes of prokinetic drugs, including their pharmacokinetic properties, efficacy, safety and tolerability and potential indications.

Advancing airway management for enhanced patient outcomes: a narrative review

Airway management evidence has primarily been gathered within the operating room, particularly during the induction of anesthesia. The introduction of newly developed supraglottic devices and videolaryngoscopes have significantly impacted the guidelines for managing difficult airways, prompting the need for new evaluation criteria. Moreover, airway complications such as accidental extubation may occur during surgery, while aspiration or respiratory suppression can manifest during the recovery period following extubation. In this review, I will explore the potential future standards for airway management and potential indications for its application. Additionally, I will underscore the significance of emergency airway management during both the surgical procedure and the recovery phase. It is imperative that we not only accumulate knowledge related to managing difficult airways but also focus on emergency airway management in the future. This calls for interprofessional airway management training for all members of the perioperative team. Key words: Airway Management; Videolaryngoscope; Supraglottic Device; Future Direction Abbreviations: DAM - Difficult Airway Management; DAS - Difficult Airway Society; OR - operating room; SGD - Supraglottic Device; VLS – videolaryngoscope Citation: Komasawa N. Advancing airway management for enhanced patient outcomes: a narrative review. Anaesth. pain intensive care 2024;28(1):171−176; DOI: 10.35975/apic.v28i1.2391 Received: December 12, 2023; Reviewed: December 16, 2023; Accepted: December 16, 2023

MRNDR: Multihead Attention-Based Recommendation Network for Drug Repurposing.

As is well-known, the process of developing new drugs is extremely expensive, whereas drug repurposing represents a promising approach to augment the efficiency of new drug development. While this method can indeed spare us from expensive drug toxicity and safety experiments, it still demands a substantial amount of time to carry out precise efficacy experiments for specific diseases, thereby consuming a significant quantity of resources. Therefore, if we can prescreen potential other indications for selected drugs, it could result in substantial cost savings. In light of this, this paper introduces a drug repurposing recommendation model called MRNDR, which stands for Multi-head attention-based Recommendation Network for Drug Repurposing. This model serves as a prediction tool for drug-disease relationships, leveraging the multihead self-attention mechanism that demonstrates robust generalization capabilities. These capabilities stem not only from our extensive million-level training data set, BioRE (Biology Recommended Entity data), but also from the utilization of the WRDS (Weighted Representation Distance Score) algorithm proposed by us. The MRNDR model has achieved new state-of-the-art results on the GP-KG public data set, with an MRR (Mean Reciprocal Rank) score of 0.308 and a Hits@10 score of 0.628. This represents significant improvements of 4.7% (MRR) and 18.1% (Hits@10) over the current best-performing models. Additionally, to further validate the practical utility of the model, we examined results recommended by MRNDR that were not present in the training data set. Some of these recommendations have undergone clinical trials, as evidenced by their presence on ClinicalTrials.gov and the China Clinical Trials Center, indirectly confirming the applicability of MRNDR. The MRNDR model can predict the reusability of candidate drugs, reducing the need for manual expert assessments and enabling efficient drug repurposing.

The Application of Cone Beam Computed Tomography (CBCT) on the Diagnosis and Management of Maxillofacial Trauma.

The assessment and management of facial trauma in an acute setting is one of the core services provided by oral and maxillofacial units in the United Kingdom. Imaging is a pre-requisite for appropriate diagnosis and treatment planning, with a combination of plain radiographs and medical-grade CT being the mainstay. However, the emergence of cone beam CT in recent years has led to its wider applications, including facial trauma assessment. It can offer multi-planar reformats and three-dimensional reconstruction at a much lower radiation dose and financial cost than conventional CT. The purpose of this review is to appraise its potential indications in all anatomical areas of maxillofacial trauma and provide our experience at a level 1 trauma centre.

State-of-the-Art of Transcatheter Left Atrial Appendage Occlusion.

Left atrial appendage occlusion (LAAO) is an increasingly used alternative to oral anticoagulation in patients with atrial fibrillation, especially in patients with absolute/relative contraindications to these therapies. This review will cover three main aspects of the procedure. In the fist part of the manuscript, we focus on patient selection. We describe three main categories of patients with primary indication to LAAO, namely patients with previous or at a high risk of intracerebral bleeding, patients with a history of major gastrointestinal bleeding and patients with end-stage renal disease and absolute contraindication to novel oral anticoagulants. Some other potential indications are also described. In the second part of the manuscript, we review available devices, trying to highlight different aspects and potential specific advantages. The last section overviews different ways for pre-, intra- and postprocedural imaging, in order to improve procedural safety and efficacy and ameliorate patient outcome. The characteristics of available contemporary devices and the role of imaging in procedural planning, intraprocedural guidance and follow-up are described.

Potential Indications of Dupilumab in Th-2 Inflammatory Disease.

Dupilumab is a fully humanized IgG4 monoclonal antibody, inhibiting IL-4 and IL-13 signaling, which are the main cytokines involved in type 2 inflammatory diseases. Its introduction was a breakthrough in the treatment of moderate-to-severe atopic dermatitis, but it is also used in other inflammatory diseases, including asthma, eosinophilic esophagitis and chronic rhinosinusitis with nasal polyposis. Recent advances in the understanding of inflammatory pathways have revealed that Th2-type inflammation is involved in a wider range of diseases than previously thought. The aim of our review is to examine off-label therapeutic indications of dupilumab, including bullous dermatoses (pemphigus, bullous pemphigoid) and alopecia areata, and to investigate its potential applications in cancer patients on anti-PD1 therapy.

A multicentric, single arm, open-label, phase I/II study evaluating PSMA targeted radionuclide therapy in adult patients with metastatic clear cell renal cancer (PRadR)

BackgroundDespite advancements in managing metastatic clear cell renal carcinoma (mccRCC) through antiangiogenic tyrosine kinase inhibitors and immunotherapy, there remains a demand for novel treatments for patients experiencing progression despite the use of these medications. There is currently no established standard treatment for patients receiving third therapy line. Prostate Specific Membrane Antigen (PSMA) whose high expression has been demonstrated in metastatic aggressive prostate adenocarcinoma is also highly expressed in neovessels of various solid tumors including renal cell carcinoma (RCC): 86% of clear cell RCC, 61% of chromophobe RCC, and 28% of papillary RCC. Therefore, PSMA may be a target expressed in metastatic ccRCC for radionuclide therapy using PSMA ligands radiolabeled with Lutetium-177 (PRLT). 177Lu-PSMA delivers ß-particle radiation to PSMA-expressing cells and the surrounding microenvironment with demonstrated efficacy in metastatic prostate cancer.MethodsThis is a multicenter phase I/II study designed to assess the tolerability and effectiveness of 177Lu-PSMA-1 in individuals with PSMA-positive metastatic clear cell renal cell carcinoma (ccRCC), identified through 68Ga-PSMA PET, conducted in France (PRadR). 48 patients will be treated with 4 cycles of 7.4 GBq of 177Lu-PSMA-1 every 6 weeks. The primary objective is to evaluate the safety of 177Lu-PSMA-1 (phase I) and the efficacy of 177Lu-PSMA-1 in mccRCC patients (phase II). Primary endpoints are incidence of Severe Toxicities (ST) occurring during the first cycle (i.e. 6 first weeks) and disease Control Rate after 24 weeks of treatment (DCR24w) as per RECIST V1.1. Secondary objective is to further document the clinical activity of 177Lu-PSMA-1 in mccRCC patients (duration of response (DoR), best overall response rate (BORR), progression fee survival (PFS) and overall survival (OS).DiscussionOur prospective study may lead to new potential indications for the use of 177Lu-PSMA-1 in mccRCC patients and should confirm the efficacy and safety of this radionuclide therapy with limited adverse events. The use of 177Lu-PSMA-1may lead to increase disease control, objective response rate and the quality of life in mccRCC patients.Trial registrationClinicalTrials.gov: NCT06059014.

An update on the current indications for in vitro maturation.

In vitro maturation has become a significant component of modern assisted reproductive techniques. Published data have been supported for the safety and effectiveness of in vitro maturation treatment. In recent years, potential indications for in vitro maturation (IVM) have been a topic of interest and investigation. Significant improvements in technique enhancement and data publication for evaluating the efficacy of IVM have been achieved. Recent studies have shown that IVM could offer several advantages over in vitro fertilization. Currently, there are growing indications for IVM beyond the commonly mentioned indication of infertile women with polycystic ovary syndrome. Additionally, some potential candidates might have significant advantages for IVM, such as women diagnosed with gonadotropin resistance ovary syndrome or those seeking fertility preservation. With a better understanding of IVM, from basic science to clinical practice, it can be applied safely, effectively, and affordably to a broader range of patients, making it a more accessible and patient-friendly option. Despite the possibly acknowledged limitations, the potential of in vitro maturation cannot be denied. As this technique becomes increasingly accessible to patients and more continuous efforts are dedicated to advancing this technique, the impact of in vitro maturation is expected.

Cannabidiol and its Potential Evidence-Based Psychiatric Benefits - A Critical Review.

The endocannabinoid system shows promise as a novel target for treating psychiatric conditions. Cannabidiol (CBD), a naturally occurring cannabinoid, has been investigated in several psychiatric conditions, with diverse effects and an excellent safety profile compared to standard treatments. Even though the body of evidence from randomised clinical trials is growing, it remains relatively limited in most indications. This review comprises a comprehensive literature search to identify clinical studies on the effects of CBD in psychiatric conditions. The literature search included case studies, case reports, observational studies, and RCTs published in English before July 27, 2023, excluding studies involving nabiximols or cannabis extracts containing CBD and ∆9-tetrahydrocannabinol. Completed studies were considered, and all authors independently assessed relevant publications.Of the 150 articles identified, 54 publications were included, covering the effects of CBD on healthy subjects and various psychiatric conditions, such as schizophrenia, substance use disorders (SUDs), anxiety, post-traumatic stress disorder (PTSD), and autism spectrum disorders. No clinical studies have been published for other potential indications, such as alcohol use disorder, borderline personality disorder, depression, dementia, and attention-deficit/hyperactivity disorder. This critical review highlights that CBD can potentially ameliorate certain psychiatric conditions, including schizophrenia, SUDs, and PTSD. However, more controlled studies and clinical trials, particularly investigating the mid- to long-term use of CBD, are required to conclusively establish its efficacy and safety in treating these conditions. The complex effects of CBD on neural activity patterns, likely by impacting the endocannabinoid system, warrant further research to reveal its therapeutic potential in psychiatry.

Role of Transporters and Enzymes in Metabolism and Distribution of 4-Chlorokynurenine (AV-101).

4-Chlorokynurenine (4-Cl-KYN, AV-101) is a prodrug of a NMDA receptor antagonist and is in clinical development for potential CNS indications. We sought to further understand the distribution and metabolism of 4-Cl-KYN, as this information might provide a strategy to enhance the clinical development of this drug. We used excretion studies in rats, in vitro transporter assays, and pharmacogenetic analysis of clinical trial data to determine how 4-Cl-KYN and metabolites are distributed. Our data indicated that a novel acetylated metabolite (N-acetyl-4-Cl-KYN) did not affect the uptake of 4-Cl-KYN across the blood-brain barrier via LAT1. 4-Cl-KYN and its metabolites were found to be renally excreted in rodents. In addition, we found that N-acetyl-4-Cl-KYN inhibited renal and hepatic transporters involved in excretion. Thus, this metabolite has the potential to limit the excretion of a range of compounds. Our pharmacogenetic analysis found that a SNP in N-acetyltransferase 8 (NAT8, rs13538) was linked to levels of N-acetyl-4-Cl-KYN relative to 4-Cl-KYN found in the plasma and that a SNP in SLC7A5 (rs28582913) was associated with the plasma levels of the active metabolite, 7-Cl-KYNA. Thus, we have a pharmacogenetics-based association for plasma drug level that could aid in the drug development of 4-Cl-KYN and have investigated the interaction of a novel metabolite with drug transporters.

Antipsychotic initiation in mechanically ventilated patients in a medical intensive care unit

Objectives: Guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients (PADIS) in the intensive care unit (ICU) promote use of analgosedation to minimize pain, reduce anxiety, and facilitate care. They also suggest against routine use of antipsychotics (APs) for delirium. Our institution’s adaptation incorporates assessment-driven, protocol-based pain, and sedation management and suggests a short course of APs in patients with agitated delirium, defined as Confusion Assessment Method for the ICU (CAM-ICU) positive with Richmond Agitation Sedation Scale (RASS) ≥ +2. While the use of APs in the ICU is typically for delirium, a recent study assessed whether quetiapine reduced sedative requirements among non-delirious patients. The purpose of this study was to assess adherence to our institutional guideline for AP use and to describe sedative and opioid use in relation to AP initiation. Materials and Methods: This retrospective study included patients who were mechanically ventilated and received ≥ 3 new start AP doses. The primary outcome was adherence to our guideline for use of APs in agitated delirium. The secondary outcomes were CAM-ICU and RASS scores in relation to AP initiation and change in sedative and analgesic infusion rates following AP initiation. Results: Thirty-eight patients were included in the study. Five had APs initiated appropriately per our guideline. There was no clinically significant change in continuous infusion rates in the 24 h before and after AP initiation. Conclusion: Overall, AP use was liberal with patients being started on APs who did not have agitated delirium, thus indicating potential alternative indications for initiation. APs did not result in a clinically significant change in continuous infusion requirements in the 24 h following initiation.

Applications of artificial intelligence in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide, despite the fact that treatment is available, and blindness can be prevented in most cases. There are two key gaps in care delivery. The first is access to care with many parts of the world underserved. The second is subjective diagnosis where the eye exam is challenging, and different clinicians may perceive different levels of severity. Multiple potential indications for use (IFUs) have been proposed for ROP AI algorithms that could impact both gaps in care. In this presentation I will review potential IFUs and the potential translational challenges in implementation.

Current pharmacotherapeutic properties of low-dose naltrexone therapy in humans and possible therapeutic and prophylactic indications in cats and dogs

Naltrexone was first developed in 1963 as an opioid antagonist for therapeutic use in opioid-dependent individuals (alcohol, narcotics, and tobacco) with a 50 mg/day dose approved by the Food and Drug Administration (FDA). In 1985, Dr. Bernard Bihari explained that when naltrexone is taken in very low doses (1-5 mg/day) before bedtime, it blocks opioid receptors for 2- 4 hours and leads to the release of endorphins in the early morning hours, serving as an opioid agonist and immunomodulatory agent. This extra endorphin secretion has been proven to enhance the immune system response in AIDS patients. Endogenous opioids that affect cell development are referred to as opioid growth factor (OGF) and met-enkephalin (ME). Low-dose-naltrexone (LDN) pharmacotherapeutically possesses immunomodulatory, anticarcinogenic, antiviral, antibacterial, antiparasitic, and antifungal properties. LDN also increases the production and sensitivity of OGF, ME, and OGF receptor (OGFr) in the bloodstream, thereby enhancing quality of life. Based on these pharmacotherapeutic properties, LDN application is believed to be effective in the treatment or prophylaxis of various infectious diseases in cats and dogs, particularly vasculitis-related diseases such as feline infectious peritonitis (FIP) and infectious canine hepatitis (ICH), hypothyroidism, gastrointestinal disorders, spondylosis, rheumatoid arthritis, autoimmune diseases, pneumonia, atopic and allergic dermatitis, pyodermas, resistant pyodermas, methicillin-resistant Staphylococcus aureus (MRSA) or various gastrointestinal disorders, alopecia, stubborn dermatomycosis, stubborn demodicosis, various geriatric and oncogenic diseases, and deep depressions or obsessive-compulsive disorders. Thus, this review aims to evaluate the pharmacotherapeutic properties of LDN therapy usage and mechanisms of action in detail and assess the potential indications in cats and dogs based on these mechanisms.

Position statement of the German STI Society on the prophylactic use of doxycycline to prevent STIs (Doxy-PEP, Doxy-PrEP).

Over the past two decades, there has been a rise in the incidence of syphilis, particularly among men who have sex with men (MSM). This has sparked interest in studying the prophylactic use of doxycycline to prevent syphilis and other sexually transmitted infections (STIs), commonly referred to as Doxycycline Pre- or Post-Exposure Prophylaxis (Doxy-PrEP, Doxy-PEP). At the same time, demand from potential users for this preventive measure is increasing. Several randomized controlled trials have demonstrated that the prophylactic use of doxycycline in MSM and trans women using HIV pre-exposure prophylaxis (HIV-PrEP) or living with an HIV infection effectively reduces the risk of syphilis and chlamydia infections. At present, however, unresolved questions remain, particularly regarding implications of a broad implementation of prophylactic doxycycline to prevent STIs on tetracycline and other antimicrobial resistance in bacterial STIs, non-STI-related bacterial pathogens, and the microbiome. In response to the increasing demand and the challenge of balancing effectiveness, safety, and the risk of promoting antibiotic resistance, the German STI Society (DSTIG) has issued a position statement, providing specific recommendations regarding potential indications, criteria, and occasions for the use of doxycycline in STI prevention. These recommendations are based on current evidence and expert opinion.

The modified Spitzy shelf acetabuloplasty for the dysplastic hip.

Although there are various pelvic osteotomies for acetabular dysplasia of the hip, shelf operations offer effective and minimally invasive osteotomy. Our study aimed to assess outcomes following modified Spitzy shelf acetabuloplasty. Between November 2000 and December 2016, we retrospectively evaluated 144 consecutive hip procedures in 122 patients a minimum of five years after undergoing modified Spitzy shelf acetabuloplasty for acetabular dysplasia including osteoarthritis (OA). Our follow-up rate was 92%. The mean age at time of surgery was 37 years (13 to 58), with a mean follow-up of 11 years (5 to 21). Advanced OA (Tönnis grade ≥ 2) was present preoperatively in 16 hips (11%). The preoperative lateral centre-edge angle ranged from -28° to 25°. Survival was determined by Kaplan-Meier analysis, using conversions to total hip arthroplasty as the endpoint. Risk factors for joint space narrowing less than 2 mm were analyzed using a Cox proportional hazards model. The mean Merle d'Aubigné clinical score improved from 11.6 points (6 to 17) preoperatively to 15.9 points (12 to 18) at the last follow-up. The survival rates were 95% (95% confidence interval (CI) 91 to 99) and 86% (95% CI 50 to 97) at ten and 15 years. Multivariate Cox regression identified three factors associated with radiological OA progression: age (hazard ratio (HR) 2.85, 95% CI 1.05 to 7.76; p = 0.0398), preoperative joint space (HR 2.41, 95% CI 1.35 to 4.29; p = 0.0029), and preoperative OA (HR 8.34, 95% CI 0.94 to 73.77; p = 0.0466). Modified Spitzy shelf acetabuloplasty is an effective joint-preserving surgery with a wide range of potential indications.

The Use of Renin-Angiotensin System Blockades Among Patients with Chronic Kidney Disease

Background and objectives: Hypertension is common in adult patients with chronic kidney disease with a prevalence that depends on the stage and etiology of chronic kidney disease and has been reported to range from 60-90%. The aim of this study was to evaluate the clinical use of renin angiotensin system blockers in chronic kidney disease patients and to identify their potential indications, contraindications and side effects amongst different clinical specialties in relation to their clinical outcomes. Methods: This study was a descriptive cross sectional based on self-administered online questionnaire, 133 medical doctors from different specialties including nephrologists, internists, urologists, general practitioners responded to the questionnaire and filled it up, which was composed of three main parts including the socio-demographic data of the participants, data about CKD and its stages and finally the RAS blockades. The study extended from June until July 2021. Results: The mean age ± standard deviation of respondents was 44.65 ± 6.89 years. Nearly one third of the respondents were internist, 12.8% nephrologist, 7.5% urologist and 45.9% from other different specialties. The vast majority (98.5%) of the physicians thought that renin angiotensin system inhibitors are effective anti-hypertensive agents even for chronic kidney disease patients. Most of the nephrologists and other specialties would continue the renin angiotensin system inhibitors while most of the internists and urologists would either stop or change the renin angiotensin system inhibitors, this was statistically significant and p–value was 0.010.

Abstract C016: Evaluating clinical biomarkers of FHD-286, a potent and selective inhibitor of BRG1/BRM, in metastatic uveal melanoma

Abstract The BRG/Brahma-associated factors (BAF) family of chromatin remodeling complexes (also referred to as the mSWI/SNF complex) regulates chromatin accessibility and gene expression through its ATP-dependent remodeling activity. FHD-286, a first-in-class compound that potently and selectively inhibits the ATPase components of the BAF complex, BRG1 and BRM, was evaluated in a Phase I dose escalation in subjects with metastatic uveal melanoma (mUM) (FHD-286-001). The pharmacodynamics of FHD-286 were assessed to demonstrate proof-of-mechanism and understand the downstream molecular and clinical impact of BRG1/BRM inhibition. In addition, circulating tumor DNA (ctDNA) was evaluated as an early predictor of overall survival benefit. Seventy-three subjects were on a daily dosing regimen ranging from 2.5 to 10 mg or an intermittent regimen of 1-week on/1-week-off ranging from 10 to 22.5 mg. Tumor biopsies were collected at screening and either Cycle 3, or end of treatment. Biomarker changes in the tumor were observed by histological assessment, by IHC/IF biomarker assays, and RNA sequencing. Observations were suggestive of a differentiation effect by FHD-286 on the tumor cells, including a decrease in stemness genes and an increase in mature melanocytic markers. Evidence of necrosis and a trend of decreasing tumor cell density were also seen. In addition, ctDNA was measured in serial plasma samples using a targeted NGS panel. A reduction in ctDNA was shown in approximately 50% of subjects, which correlated with an increased overall survival benefit. Lastly, serial blood samples collected in Paxgene RNA tubes were analyzed by RNA sequencing. A robust dose-dependent gene signature was identified as a peripheral readout of target engagement at steady-state in both dosing regimens and across dose cohorts. In summary, we observed changes in the tumor cells at the biopsy site and ctDNA that suggest FHD-286 has a biological impact on uveal melanoma that may lead to clinical benefit. Given the limitations and challenges to obtain tumor biopsies from every subject and at a frequent rate, the identified PD gene signature in the blood is a valuable tool to measure target engagement in this study, and other potential solid tumor indications. Citation Format: Jessica Wan, Kim Horrigan, GiNell Elliott, Liv Johannessen, Mike Collins, Alexander J. Lazar, Dillon Corrigan, Caitlin Patriquin, Sam Agresta, Jessica Piel, Martin Hentemann. Evaluating clinical biomarkers of FHD-286, a potent and selective inhibitor of BRG1/BRM, in metastatic uveal melanoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C016.

IBC-Oxford University2023_BJSOral_20Video Presentation: Fundectomy and Indocyanine green fluorescence angiography in revisional laparoscopic Roux-en-Y gastric bypass

Abstract Introduction Revisional bariatric procedures are increasingly prevalent. These procedures are more complex with higher risk of complications as compared to primary procedures. The potential indications for revisional laparoscopic gastric bypass (R-LRYGB) may include weight regain and gastroesophageal reflux disease (GORD). This video abstract presents role of fundectomy and Indocyanine green fluorescence angiography (ICG-FA) for perfusion assessment of gastric pouch in R-LRYGB. Methods and Operative technique A 40-year-old female with previous laparoscopic adjustable gastric band (LAGB) surgery underwent R-LRYGB procedure following approval at bariatric multidisciplinary team meeting. LAGB was removed due to band slippage and chronic pouch dilatation, 2 years prior to the revisional procedure. Preoperative BMI was 53 kg/m2. Pre-operative upper gastrointestinal endoscopy was normal. The operative technique included dissection of angle of His, access into lesser sac along lesser curve below 2nd vessel off left gastric artery (LGA) and division of short gastric vessels to gain access to leaser sac from lateral aspect. The stomach was divided horizontally with linear stapler (EndoGIA 60 Gold cartridge), level with second vessel off LGA followed by creation of vertical gastric pouch over a size 34 Oro-gastric tube, that included excision of gastric fundus. ICG was administered intravenously according to an agreed protocol for the study. Karl Storz Image1 STM Rubina system with overlay and monochromatic modes was used for perfusion assessment. ICG-FA was utilised for qualitative assessment of gastric pouch perfusion before and after linear stapled gastro-jejunal anastomosis. Results Operative time was 240 minutes. Adhesions were encountered in the lesser sac at the site of previous LAGB. Fundectomy allowed better visualisation of lesser sac, adhesiolysis and facilitated creation of gastric pouch. ICG perfusion of gastric pouch was satisfactory. The postoperative length of stay was 2 days. There were nopostoperative complications at 6 months follow-up. The patient achieved 42% excess weight loss (BMI 43) over 6 months period. Conclusions Fundectomy is a safe and feasible operative step in R-LRYGB in patients with previous primary LAGB. ICG-FA is a promising qualitative assessment tool in revisional bariatric procedures.

Abstract C071: From promise to progress: Utilizing the All of Us dataset to advance cancer disparities research

Abstract As the world’s largest and most diverse dataset of its kind, the All of Us Research Program within the National Institutes of Health is a national effort that is building the largest, most diverse health information database that researchers can use to study how different genetic, lifestyle, and environmental factors impact health and disease. All of Us is built in partnership with participants spanning different ages, races, ethnicities, and regions of the country, including 45% who self-identify as racial and ethnic minorities and 75% from communities underrepresented in biomedical research (UBR). In addition to contributing to health research, participants are active partners of the program through participation in the program’s governance and ongoing engagement within the Engagement Ecosystem ‒ a network of national partners with deep connections to communities. These partners work collaboratively to reach specific populations by raising awareness about the program among racial/ethnic minority populations and historically underrepresented communities, such as LGBGTQIA+, disability communities, and rural and older adults, in an effort to complement and enhance existing outreach and engagement efforts.As of April 2023, the program has data from 413,450+ participants, containing the largest set of whole genome sequences (WGS) widely available for research with over 312,900 genotyping arrays, 245,350 WGS, and 1,000 long-read sequences available to registered researchers. To ensure value is returned, participants may consent to receiving a personalized DNA report with information on genetic ancestry, traits, pharmacogenetics, and a hereditary disease risk report on the ACMG 59 “medically actionable” genes, with 20 genes related to some type of cancer. The most common conditions available include cancer, cardiovascular disease, hypertension, mental health, and diabetes. There is also electronic health record (EHR) data from more than 287,000 participants inclusive of demographics, health care visits, diagnoses, and medications data, with over 50,700 diagnosed with at least one type of cancer. As many cancer disparities are driven by the interaction of biological and social factors, All of Us provides an opportunity for researchers to explore data on lifestyle factors, social determinants of health, 3-digit zip codes, neighborhood, social life and exposures, including potential indications of allostatic load and inflammatory markers associated with stress and discrimination, as well as factors related to tobacco and alcohol use. Using a broad search for cancer diagnoses in participant EHR records, there are over 200 different kinds of cancers with 73% represented in the UBR race/ethnicity category. Session attendees will gain a better understanding of the breadth and depth of data available to study within the Researcher Workbench, learn how this data can support cancer intervention research, and recognize the utility of accessing the world’s largest, most diverse dataset and its role in addressing health disparities. Citation Format: Karriem S. Watson, Martin Mendoza, Grant Jones, Sydney McMaster, Anna Mitiku. From promise to progress: Utilizing the All of Us dataset to advance cancer disparities research [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C071.

Surface water environmental carrying capacity and surface water quality based on economy-society-environment nexus – Evidence from China

Impacts of economy-society-environment on surface water resource in China are complex and unclear. Revealing these connections is vital to understand responses of surface water quality to anthropogenic activities. This study made an attempt to explore potential indications on surface water quality from economic, social and environmental factors in eight separate regions of China during the period of 2000–2019. Five machine learning models were employed including Greedy Thick Thinning Bayesian Belief Network, Naive Bayes, Augmented Naive Bayes (ANB), Logistic Regression and Random Forest. A total of 8 economic variables, 5 social variables and 8 environmental variables were introduced into the models. Results showed that ANB presented the best performance in estimating the surface water quality class with the highest accuracies of 81%, 75% and 87% for three surface water quality groups (Class I–III, Class IV–V and worse than Class V), respectively. The higher the surface water environmental carrying capacity in a region, the better the estimation performance of ANB on the surface water quality class. Surface water quality with Class I–III was more closely related to economic and social development, while environmental variables largely interpreted the quality of surface water with Class IV–V in most regions. The critical factors filtered by the importance analysis were indicative on surface water quality. This study provided a feasible framework in revealing the economy-society-environment nexus in the context of comprehensive management on regional surface water quality.