Quantitative 23Na magnetic resonance imaging in the abdomen at 3 T.

OBJECTIVES: To assess the feasibility of sodium-23 MRI for performing quantitative and non-invasive measurements of total sodium concentration (TSC) and relaxation in a variety of abdominal organs. MATERIALS AND METHODS: Proton and sodium imaging of the abdomen was performed in 19 healthy volunteers using a 3D cones sequence and a sodium-tuned 4-rung transmit/receive body coil on a clinical 3 T system. The effects of B1 non-uniformity on TSC measurements were corrected using the double-angle method. The long-component of 23Na T2* relaxation time was measured using a series of variable echo-times. RESULTS: The mean and standard deviation of TSC and long-component 23Na T2* values were calculated across the healthy volunteer group in the kidneys, cerebrospinal fluid (CSF), liver, gallbladder, spleen, aorta, and inferior vena cava. DISCUSSION: Mean TSC values in the kidneys, liver, and spleen were similar to those reported using 23Na-MRI previously in the literature. Measurements in the CSF and gallbladder were lower, potentially due to the reduced spatial resolution achievable in a clinically acceptable scan time. Mean long-component 23Na T2* values were consistent with previous reports from the kidneys and CSF. Intra-population standard error was larger in smaller, fluid-filled structures due to fluid motion and partial volume effects.

A Data-Driven Approach to Defining Risk-Adjusted Coding Specificity Metrics for a Large U.S. Dementia Patient Cohort.

Medical coding impacts patient care quality, payor reimbursement, and system reliability through the precision of patient information documentation. Inadequate coding specificity can have significant consequences at administrative and patient levels. Models to identify and/or enhance coding specificity practices are needed. Clinical records are not always available, complete, or homogeneous, and clinically driven metrics to assess medical practices are not logistically feasible at the population level, particularly in non-centralized healthcare delivery systems and/or for those who only have access to claims data. Data-driven approaches that incorporate all available information are needed to explore coding specificity practices. Using N = 487,775 hospitalization records of individuals diagnosed with dementia and discharged in 2022 from a large all-payor administrative claims dataset, we fitted logistic regression models using patient and facility characteristics to explain the coding specificity of principal and secondary diagnoses of dementia. A two-step approach was produced to allow for the flexible clustering of patient-level outcomes. Model outcomes were then used within a Poisson binomial model to identify facilities that over- or under-specify dementia diagnoses against healthcare industry standards across hospitalizations. The results indicate that multiple factors are significantly associated with dementia coding specificity, especially for principal diagnoses of dementia (AUC = 0.727). The practical use of this novel risk-adjusted metric is demonstrated for a sample of facilities and geospatially via a U.S. map. This study's findings provide healthcare facilities with a benchmark for assessing coding specificity practices and developing quality enhancements to align with healthcare industry standards, ultimately contributing to better patient care and healthcare system reliability.

Cardiovascular and mortality benefits of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists as third-step glucose-lowering medicine in patients with type 2 diabetes: a retrospective cohort analysis.

INTRODUCTION: Studies have found that sodium-glucose cotransporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP1) have cardiovascular benefits for patients with type 2 diabetes (DM2) and atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF). The literature does not provide evidence specifically for patients with these conditions who are adding one of these medicines to two glucose-lowering medications (ie, as "third-step" therapy). We explored the effects of different third-step medications on cardiovascular outcomes in patients with diabetes and these comorbid conditions. Specifically, we compared third-step SGLT2 or GLP1 to third-step dipeptidyl peptidase-4 inhibitors (DPP4), insulin, or thiazolidinediones (TZD). RESEARCH DESIGN AND METHODS: We assembled a retrospective cohort of adults at five Kaiser Permanente sites with DM2 and ASCVD, CKD, or HF, initiating third-step treatment between 2016 and 2020. Propensity score weighted Poisson models were used to calculate adjusted rate ratios (ARRs) for all-cause mortality, incident major adverse cardiovascular event (MACE), and incident HF hospitalization in patients initiating SGLT2 or GLP1 compared with DPP4, insulin, or TZD. RESULTS: We identified 27 542 patients initiating third-step treatment with one or more of these conditions (19 958 with ASCVD, 14 577 with CKD, and 3919 with HF). ARRs for GLP1 and SGLT2 versus DPP4, insulin, and TZD in the patient subgroups ranged between 0.22 and 0.55 for all-cause mortality, 0.38 and 0.81 for MACE, and 0.46 and 1.05 for HF hospitalization. Many ARRs were statistically significant, and all significant ARRs showed a benefit (ARR <1) for GLP1 or SGLT2 when compared with DPP4, insulin, or TZD. CONCLUSIONS: Third-step SGLT2 and GLP1 are generally associated with a benefit for these outcomes in these patient groups when compared with third-step DPP4, insulin, or TZD. Our results add to evidence of a cardiovascular benefit of SGLT2 and GLP1 and could inform clinical guidelines for choosing third-step diabetes treatment.

Modifying platelets at their birth: anti-thrombotic therapy without haemorrhage.

Cardiovascular disease is a leading cause of death. The current approach to the prevention of arterial thrombosis in cardiovascular disease is dependent on the use of therapies which inhibit the activation of platelets. Predictably these are associated with an increased risk of haemorrhage which causes significant morbidity. The thrombotic potential of an activated platelet is modifiable; being determined before thrombopoiesis. Increased megakaryocyte ploidy is associated with larger and more active platelets carrying an increased risk of thrombosis. The reduction in the ploidy of megakaryocytes is therefore a novel area of therapeutic interest for reducing thrombosis. We propose a new therapeutic approach for the prevention and treatment of thrombosis by targeting the reduction in ploidy of megakaryocytes. We examine the role of a receptor mediated event causing megakaryocytes to increase ploidy, the potential for targeting the molecular mechanisms underpinning megakaryocyte endomitosis and the existence of two separate regulatory pathways to maintain haemostasis by altering the thrombotic potential of platelets as targets for novel therapeutic approaches producing haemostatically competent platelets which are not prothrombotic.

Two Cases of Sporadic Amyotrophic Lateral Sclerosis With Contrasting Clinical Phenotypes: Genetic Insights.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disease that affects individuals of diverse racial and ethnic backgrounds. There is currently no cure for ALS, and the number of efficient disease-modifying drugs for ALS is limited to a few, despite the large number of clinical trials conducted in recent years. The latter could be attributed to the significant heterogeneity of ALS clinical phenotypes even in their familial forms. To address this issue, we conducted postmortem genetic screening of two female patients with sporadic ALS (sALS) and contrasting clinical phenotypes. The results demonstrated that despite their contrasting clinical phenotypes, both patients had rare pathologic/deleterious mutations in five genes: ACSM5, BBS12, HLA-DQB1, MUC20, and OBSCN, with mutations in three of those genes being identical: BBS12, HLA-DQB1, and MUC20. Additional groups of mutated genes linked to ALS, other neurologic disorders, and ALS-related pathologies were also identified. These data are consistent with a hypothesis that an individual could be primed for ALS via mutations in a specific set of genes not directly linked to ALS. The disease could be initiated by a concerted action of several mutated genes linked to ALS and the disease's clinical phenotype will evolve further through accessory gene mutations associated with other neurological disorders and ALS-related pathologies.

Stabilizing tumor resident mast cells restores T cell infiltration and sensitizes sarcomas to PD-L1 inhibition.

PURPOSE: To explore the cellular crosstalk of tumor resident mast cells (MCs) in controlling the activity of cancer-associated fibroblasts (CAFs) to overcome TME abnormalities, enhancing the efficacy of immune checkpoint inhibitors (ICIs) in sarcoma. EXPERIMENTAL DESIGN: We used a coculture system followed by further validation in mouse models of fibrosarcoma and osteosarcoma with or without administration of the MC stabilizer and antihistamine ketotifen. To evaluate the contribution of ketotifen in sensitizing tumors to therapy, we performed combination studies with doxorubicin chemotherapy and anti-PD-L1 (B7-H1, clone 10F.9G2) treatment. We investigated the ability of ketotifen to modulate the TME in human sarcomas in the context of a repurpose phase II clinical trial. RESULTS: Inhibition of MC activation with ketotifen successfully suppressed CAF proliferation and stiffness of the extracellular matrix accompanied by an increase in vessel perfusion in fibrosarcoma and osteosarcoma as indicated by ultrasound shear wave elastography imaging. The improved tissue oxygenation increased the efficacy of chemo-immunotherapy, supported by enhanced T cell infiltration and acquisition of tumor antigen-specific memory. Importantly, the effect of ketotifen in reducing tumor stiffness was further validated in sarcoma patients highlighting its translational potential. CONCLUSIONS: Our study suggests the targeting of MCs with clinically administered drugs, such as antihistamines, as a promising approach to overcome resistance to immunotherapy in sarcomas.

Screening of Diverse Lupinus spp. Highlights New Resistances to Sclerotinia sclerotiorum.

Stem rot caused by Sclerotinia sclerotiorum is a serious, and sometimes devastating, disease of lupin (Lupinus spp.). Two hundred and thirty-six lupin accessions from across 12 Lupinus species were screened against the prevalent S. sclerotiorum isolate MBRS-1 (pathotype 76). L. angustifolius accession 21655 and L. albus var. albus accession 20589 showed immune and 'near-immune' responses, respectively. Thirteen accessions of L. angustifolius, three accessions each of L. albus and L. albus var. albus, and a single accession each of L. albus var. graecus, L. mutabilis, L. palaestinus and L. pilosus (totalling ~4%) showed a highly resistant (HR) response. A further 19 accessions of L. angustifolius, two accessions each of L. albus and L. pilosus, and a single accession of L. mutabilis (totalling ~10%) showed a resistant (R) response. The reactions of 16 (15 L. angustifolius, one L. digitatus) of these 236 accessions were also compared with their reactions to a different isolate, WW-3 (pathotype 10). Against this isolate, five L. angustifolius accessions showed a HR response and four showed a R response, and the L. digitatus accession showed a moderate resistance (MR) response. Overall, isolate WW-3 caused significantly (P<0.05) smaller lesions than MBRS-1 across tested accessions in common. In addition, 328 plants in a 'wild' naturalized field population of L. cosentini were screened in situ in the field against isolate MBRS-1. Five (~1.5%) of the 328 plants of wild lupin showed an immune response, 63 (~19%) showed a HR response, and 146 (~45%) showed a R response. We believe this is the first examination of diverse Lupinus spp. germplasm responses to a prevalent pathotype of S. sclerotiorum. Lupin genotypes exhibiting high level resistance to Sclerotinia stem rot identified in this study can now be used as parental lines for crosses in lupin breeding programs and/or directly as improved cultivars to reduce the adverse impact of this disease on lupin crops.

Impact of the COVID-19 pandemic on the productivity and career prospects of musculoskeletal researchers.

Academic researchers faced a multitude of challenges posed by the COVID-19 pandemic, including widespread shelter-in-place orders, workplace closures, and cessation of in-person meetings and laboratory activities. The extent to which these challenges impacted musculoskeletal researchers, specifically, is unknown. We developed an anonymous web-based survey to determine the pandemic's impact on research productivity and career prospects among musculoskeletal research trainees and faculty. There were 116 musculoskeletal (MSK) researchers with varying demographic backgrounds who completed the survey. Of respondents, 48.3% (n = 56) believed that musculoskeletal funding opportunities decreased because of COVID-19, with faculty members more likely to hold this belief compared to nonfaculty researchers (p = 0.008). Amongst MSK researchers, 88.8% (n = 103) reported research activity was limited by COVID-19, and 92.2% (n = 107) of researchers reported their research was not able to be refocused on COVID-19-related topics, with basic science researchers less likely to be able to refocus their research compared to clinical researchers (p = 0.030). Additionally, 47.4% (n = 55) reported a decrease in manuscript submissions since the onset of the pandemic. Amongst 51 trainee researchers, 62.8% (n = 32) reported a decrease in job satisfaction directly attributable to the COVID-19 pandemic. In summary, study findings indicated that MSK researchers struggled to overcome challenges imposed by the pandemic, reporting declines in funding opportunities, research productivity, and manuscript submission. Trainee researchers experienced significant disruptions to critical research activities and worsening job satisfaction. Our findings motivate future efforts to support trainees in developing their careers and target the recovery of MSK research from the pandemic stall.

Development and translation of thiometallate sulfide donors using a porcine model of coronary occlusion and reperfusion.

Sulfide-releasing compounds reduce reperfusion injury by decreasing mitochondria-derived reactive oxygen species production. We previously characterised ammonium tetrathiomolybdate (ATTM), a clinically used copper chelator, as a sulfide donor in rodents. Here we assessed translation to large mammals prior to clinical testing. In healthy pigs an intravenous ATTM dose escalation revealed a reproducible pharmacokinetic/pharmacodynamic (PK/PD) relationship with minimal adverse clinical or biochemical events. In a myocardial infarction (1-h occlusion of the left anterior descending coronary artery)-reperfusion model, intravenous ATTM or saline was commenced just prior to reperfusion. ATTM protected the heart (24-h histological examination) in a drug-exposure-dependent manner (r2 = 0.58, p < 0.05). Blood troponin T levels were significantly (p < 0.05) lower in ATTM-treated animals while myocardial glutathione peroxidase activity, an antioxidant selenoprotein, was elevated (p < 0.05). Overall, our study represents a significant advance in the development of sulfides as therapeutics and underlines the potential of ATTM as a novel adjunct therapy for reperfusion injury. Mechanistically, our study suggests that modulating selenoprotein activity could represent an additional mode of action of sulfide-releasing drugs.

Not so Fast: Extended Oral Antibiotic Prophylaxis Does Not Reduce 90-Day Infection Rate Following Joint Arthroplasty.

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication following both total hip (THA) and knee (TKA) arthroplasty. Extended oral antibiotic (EOA) prophylaxis has been reported to reduce PJI following TJA in high-risk patients. The purpose of this study was to determine if EOA reduces PJI in all-comers and high-risk THA and TKA populations. METHODS: This is a retrospective cohort study, including 4,576 patients undergoing primary THA or TKA at a single institution from 2018 to 2022. Beginning in 2020, EOA prophylaxis was administered for 10 days following THA or TKA at our institution. Patients were separated into 2 cohorts (1,769 EOA, 2,807 no EOA) based on whether they received postoperative EOA. The 90-day and 1-year outcomes, with a focus on PJI, were then compared between groups. A subgroup analysis of high-risk patients was also performed. RESULTS: There was no difference in 90-day PJI rates between cohorts (EOA 1 versus no EOA 0.8%; P = .6). The difference in the rate of PJI remained insignificant at 1 year (EOA 1 versus no EOA 1%; P = .9). Similarly, our subgroup analysis of high-risk patients demonstrated no difference in postoperative PJI between EOA (n = 254) and no EOA (n = 396) (0.8 versus 2.3%, respectively; P = .2). Reassuringly, we also found no differences in the incidence of Clostridium difficile infection (EOA 0.1 versus no EOA 0.1%; P > .9) or in antibiotic resistance among those who developed PJI within 90 days (EOA 59 versus no EOA 83%; P = .2). CONCLUSIONS: With the numbers available for analysis, EOA prophylaxis was not associated with PJI risk reduction following primary TJA when universally deployed. Furthermore, among high-risk patients, there was no statistically significant difference. While we did not identify increased antibiotic resistance or Clostridium difficile infection, we cannot recommend wide-spread adoption of EOA prophylaxis, and clarification regarding the role of EOA, even in high-risk patients, is needed.

Population trends in the vulnerable Grey-headed flying-fox, Pteropus poliocephalus; results from a long-term, range-wide study.

Monitoring is necessary for the management of any threatened species if its predicament and status are to improve. Monitoring establishes baseline data for tracking trends in distribution and abundance and is a key tool for informing threatened species management. Across much of the Old World, bats in the genus Pteropus (Pteropodidae, Chiroptera) face significant threats from habitat loss, conflict with humans, and hunting. Despite conflict with humans and their threatened status, few Pteropus are being monitored. Often, this is because of difficulties associated with their high mobility, large and easily disturbed aggregations, and their use of unknown or remote habitat. Here we describe 10 years of results from the National Flying-fox Monitoring Program (NFFMP) for the grey-headed flying-fox, (Pteropus poliocephalus) in Australia. Range-wide quarterly surveys were conducted over a three-day period since November 2012 using standardized methods appropriate to conditions encountered at each roost. For our analysis of the population and its trend, we used a state-space model to account for the ecology of the grey-headed flying-fox and the errors associated with the surveying process. Despite the general perception that the species is in decline, our raw data and the modelled population trend suggest the grey-headed flying-fox population has remained stable during the NFFMP period, with the range also stable. These results indicate that the species' extreme mobility and broad diet bestow it with a high level of resilience to various disturbance events. Long-term, range-wide studies such as this one, are crucial for understanding relatively long-lived and highly nomadic species such as the grey-headed flying-fox. The outcomes of this study highlight the need for such systematic population monitoring of all threatened Pteropus species.

Machine learning-based prediction of hip joint moment in healthy subjects, patients and post-operative subjects.

The application of machine learning in the field of motion capture research is growing rapidly. The purpose of the study is to implement a long-short term memory (LSTM) model able to predict sagittal plane hip joint moment (HJM) across three distinct cohorts (healthy controls, patients and post-operative patients) starting from 3D motion capture and force data. Statistical parametric mapping with paired samples t-test was performed to compare machine learning and inverse dynamics HJM predicted values, with the latter used as gold standard. The results demonstrated favorable model performance on each of the three cohorts, showcasing its ability to successfully generalize predictions across diverse cohorts.

A Novel Method for Assessing Risk-Adjusted Diagnostic Coding Specificity for Depression Using a U.S. Cohort of over One Million Patients.

Depression is a prevalent and debilitating mental health condition that poses significant challenges for healthcare providers, researchers, and policymakers. The diagnostic coding specificity of depression is crucial for improving patient care, resource allocation, and health outcomes. We propose a novel approach to assess risk-adjusted coding specificity for individuals diagnosed with depression using a vast cohort of over one million inpatient hospitalizations in the United States. Considering various clinical, demographic, and socioeconomic characteristics, we develop a risk-adjusted model that assesses diagnostic coding specificity. Results demonstrate that risk-adjustment is necessary and useful to explain variability in the coding specificity of principal (AUC = 0.76) and secondary (AUC = 0.69) diagnoses. Our approach combines a multivariate logistic regression at the patient hospitalization level to extract risk-adjusted probabilities of specificity with a Poisson Binomial approach at the facility level. This method can be used to identify healthcare facilities that over- and under-specify diagnostic coding when compared to peer-defined standards of practice.

The identification of small molecule inhibitors with anthelmintic activities that target conserved proteins among ruminant gastrointestinal nematodes.

Gastrointestinal nematode (GIN) infections are a major concern for the ruminant industry worldwide and result in significant production losses. Naturally occurring polyparasitism and increasing drug resistance that potentiate disease outcomes are observed among the most prevalent GINs of veterinary importance. Within the five major taxonomic clades, clade Va represents a group of GINs that predominantly affect the abomasum or small intestine of ruminants. However, the development of effective broad-spectrum anthelmintics against ruminant clade Va GINs has been challenged by a lack of comprehensive druggable genome resources. Here, we first assembled draft genomes for three clade Va species (Cooperia oncophora, Trichostrongylus colubriformis, and Ostertagia ostertagi) and compared them with closely related ruminant GINs. Genome-wide phylogenetic reconstruction showed a relationship among ruminant GINs structured by taxonomic classification. Orthogroup (OG) inference and functional enrichment analyses identified 220 clade Va-specific and Va-conserved OGs, enriched for functions related to cell cycle and cellular senescence. Further transcriptomic analysis identified 61 taxonomically and functionally conserved clade Va OGs that may function as drug targets for new broad-spectrum anthelmintics. Chemogenomic screening identified 11 compounds targeting homologs of these OGs, thus having potential anthelmintic activity. In in vitro phenotypic assays, three kinase inhibitors (digitoxigenin, K-252a, and staurosporine) exhibited broad-spectrum anthelmintic activities against clade Va GINs by obstructing the motility of exsheathed L3 (xL3) or molting of xL3 to L4. These results demonstrate valuable applications of the new ruminant GIN genomes in gaining better insights into their life cycles and offer a contemporary approach to discovering the next generation of anthelmintics.IMPORTANCEGastrointestinal nematode (GIN) infections in ruminants are caused by parasites that inhibit normal function in the digestive tract of cattle, sheep, and goats, thereby causing morbidity and mortality. Coinfection and increasing drug resistance to current therapeutic agents will continue to worsen disease outcomes and impose significant production losses on domestic livestock producers worldwide. In combination with ongoing therapeutic efforts, advancing the discovery of new drugs with novel modes of action is critical for better controlling GIN infections. The significance of this study is in assembling and characterizing new GIN genomes of Cooperia oncophora, Ostertagia ostertagi, and Trichostrongylus colubriformis for facilitating a multi-omics approach to identify novel, biologically conserved drug targets for five major GINs of veterinary importance. With this information, we were then able to demonstrate the potential of commercially available compounds as new anthelmintics.

Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

Discovery and SAR Study of Boronic Acid-Based Selective PDE3B Inhibitors from a Novel DNA-Encoded Library.

Human genetic evidence shows that PDE3B is associated with metabolic and dyslipidemia phenotypes. A number of PDE3 family selective inhibitors have been approved by the FDA for various indications; however, given the undesirable proarrhythmic effects in the heart, selectivity for PDE3B inhibition over closely related family members (such as PDE3A; 48% identity) is a critical consideration for development of PDE3B therapeutics. Selectivity for PDE3B over PDE3A may be achieved in a variety of ways, including properties intrinsic to the compound or tissue-selective targeting. The high (>95%) active site homology between PDE3A and B represents a massive obstacle for obtaining selectivity at the active site; however, utilization of libraries with high molecular diversity in high throughput screens may uncover selective chemical matter. Herein, we employed a DNA-encoded library screen to identify PDE3B-selective inhibitors and identified potent and selective boronic acid compounds bound at the active site.

Assessment of owner perceptions of caregiver burden, veterinarian-client relationship and satisfaction with the provider in canine pruritus: An experimental vignette study.

BACKGROUND: Complicated treatments for skin disease are linked to owner-caregiver burden and poorer perception of the veterinarian-client relationship, regardless of disease severity. HYPOTHESES/OBJECTIVES: Using experimental vignettes, we explored the impact on owner perception of the interaction of treatment complexity and skin disease outcomes. We hypothesised that: (i) vignette conditions involving injection therapy would result in lower burden, better veterinary-client relationship and greater satisfaction relative to multimodal therapy conditions; (ii) the vignette condition of injection therapy with a completely effective outcome would be superior to all other conditions; (iii) ineffective vignette conditions would be inferior to all other conditions; and (iv) the vignette condition injection with a mostly effective outcome would be similar or superior to the multimodal therapy with a completely effective outcome condition. PARTICIPANTS: Three hundred and nine owners of pruritic dogs recruited from a general veterinary practice, pet-related podcast, or social media dog allergy group. MATERIALS AND METHODS: Participants were presented with six counterbalanced online vignettes representing three levels of treatment effectiveness (Completely Effective, Mostly Effective, Ineffective) and two treatment regimens (Multimodal, Injection). Measurements of participant perceptions of caregiver burden, veterinarian-client relationship and satisfaction were recorded. RESULTS: Injection with perfect outcome was superior to other conditions (p < 0.001). Conditions with poor effectiveness were inferior (p < 0.001). Comparison of Injection with a mostly effective outcome to Multimodal treatment with perfect outcome yielded small-to-medium effects of preference for the latter in veterinarian-client relationship and satisfaction (p < 0.01); no difference was observed for caregiver burden. When good effectiveness was assured, injection was preferred (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: Owners preferred a Completely Effective outcome and were prepared to select the Injection regimen or Multimodal therapy to achieve this; Injection was preferred when effectiveness was assured.

Endoscopic retrograde cholangiopancreatography (ERCP) approach for patients with Roux-en-Y gastric bypass: a comparative study between four ERCP techniques with proposed management algorithm.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients with Roux-en-Y gastric bypass (RYGB) due to altered anatomy. OBJECTIVE: To compare the procedural and clinical outcomes of 4 different ERCP techniques in RYGB patients. SETTING: Academic tertiary referral center in the United States. METHODS: A retrospective cohort study including patients with RYGB anatomy who underwent an ERCP between January 2015 and September 2020. We compared procedural success and adverse events (AEs) rates of balloon-assisted enteroscopy (BAE), gastrostomy-assisted ERCP (GAE), endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE), and rendezvous guidewire-assisted ERCP (RGA). RESULTS: Seventy-eight RYGB patients underwent a total of 132 ERCPs. The mean age was 60 ± 11.8 years, with female predominance (85.7%). The ERCP procedures performed were BAE (n = 64; 48.5%), GAE (n = 18; 13.7%), EDGE (n = 25; 18.9%), and RGA (n = 25; 18.9%), with overall procedure success rates of 64.1%, 100%, 89.5%, and 91.7%, respectively. All approaches were superior to BAE (GAE versus BAE, P = .003; EDGE versus BAE, P = .034; RGA versus BAE, P = .011). The overall AE rates were 10.9%, 11.1%, 15.8 %, and 25.0%, respectively. There was no statistical difference in AEs. There were also no differences in bleeding, post-ERCP pancreatitis, and perforation rates between the 4 approaches. CONCLUSION: Procedure success was similar between GAE, RGA, and EDGE, but superior to BAE. AE rates were similar between approaches.