Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice.

AIMS: Endothelin-1 (ET-1) is elevated in patients with obesity and adipose tissue of obese mice fed high-fat diet (HFD); however, its contribution to the pathophysiology of obesity is not fully understood. Genetic loss of endothelin type B receptors (ETB) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ETB activation on adipocytes may contribute to obesity pathophysiology. We hypothesized that elevated ET-1 in obesity promotes insulin resistance by reducing the secretion of insulin sensitizing adipokines, via ETB receptor. METHODS: Male adipocyte-specific ETB receptor knockout (adETBKO), overexpression (adETBOX), or control littermates were fed either normal diet (NMD) or high-fat diet (HFD) for 8 weeks. RESULTS: RNA-sequencing of epididymal adipose (eWAT) indicated differential expression of over 5500 genes (p < 0.05) in HFD compared to NMD controls, and changes in 1077 of these genes were attenuated in HFD adETBKO mice. KEGG analysis indicated significant increase in metabolic signaling pathway. HFD adETBKO mice had significantly improved glucose and insulin tolerance compared to HFD control. In addition, adETBKO attenuated changes in plasma adiponectin, insulin, and leptin that is observed in HFD versus NMD control mice. Treatment of primary adipocytes with ET-1 caused a reduction in adiponectin production that was attenuated in cells pretreated with an ETB antagonist. CONCLUSION: These data indicate elevated ET-1 in adipose tissue of mice fed HFD inhibits adiponectin production and causes insulin resistance through activation of the ETB receptor on adipocytes.

Bowel Perforation Caused by Biliary Stent Migration After ERCP: A Systematic Review.

GOALS: This systematic review aims to evaluate the risk factors, clinical features, and outcomes of bowel perforation caused by stent migration after endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUND: Distal migration of biliary stents can occur after ERCP. Upon migration, most stents pass through the intestine without adverse events; however, bowel perforation has been reported. STUDY: A comprehensive literature search of PubMed, EMBASE, and Cochrane databases was conducted through October 2023 for articles that reported bowel perforation because of stent migration. Cases of incomplete stent migration and proximal stent migration were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines to identify full-length articles in English reporting. RESULTS: Of 2041 articles retrieved on the initial search, 92 met the inclusion criteria. A total of 132 cases of bowel perforation occurred due to stent migration after ERCP (56.1% female; average age: 66 y). The median time from initial ERCP to perforation was 44.5 days (IQR 12.5-125.5). Most cases of perforation occurred in the small bowel (64.4%) compared with the colon (34.8%). Stents were mostly plastic (87.1%) with a median diameter of 10 Fr (IQR 8.5-10) and median length of 10.3 cm (IQR 715). Surgical management was pursued in 52.3% and endoscopic management in 42.4%. Bowel resection was required for 25.8% of patients. The overall mortality rate was 17.4%. CONCLUSION: In summary, this study demonstrates that bowel perforation after ERCP stent migration primarily occurs within 44.5 days and most frequently with a 10 Fr plastic biliary stent. The overall mortality rate was 17.4%. It is important for endoscopists to be mindful of this rare but serious adverse event.

Single-center experience with intraprocedural cleansing system to improve inadequate bowel preparation during colonoscopy.

Inadequate bowel preparation is common despite various preprocedure interventions. There is a need for an intervention at the time of colonoscopy to combat poor preparation. In this retrospective, observational study of 46 patients, we evaluated the clinical efficacy and feasibility of implementing the third generation of the Pure-Vu EVS System, a US Food and Drug Administration-cleared over-the-scope-based intraprocedural cleansing device, into our practice at the Minneapolis VA Medical Center (Minneapolis, Minnesota, United States). To study clinical efficacy, we measured bowel preparation adequacy before and after using the device, as measured by the Boston Bowel Preparation Score, and reviewed colonoscopy surveillance interval recommendations. Technical success and feasibility of using the device were measured by procedure success rates and duration. We found that BBPS scores increased from 4.4 to 7.9 when using the device. Technical success was achieved 78.3% of the time (36/46 cases). Median colonoscopy duration was 46 minutes, although there was a trend toward shorter procedures over time. This is the first clinical evaluation of the third generation of an intraprocedural cleansing device. We found the device efficacious and easy to use with low procedure failure rates, but it does come with a learning curve. We suspect that adoption of this device mutually will benefit patients and health systems with the potential to improve resource utilization.

A systematic review of validity of US survey measures for assessing substance use and substance use disorders.

BACKGROUND: The steep rise in substance use and substance use disorder (SUD) shows an urgency to assess its prevalence using valid measures. This systematic review summarizes the validity of measures to assess the prevalence of substance use and SUD in the US estimated in population and sub-population-based surveys. METHODS: A literature search was performed using nine online databases. Studies were included in the review if they were published in English and tested the validity of substance use and SUD measures among US adults at the general or sub-population level. Independent reviews were conducted by the authors to complete data synthesis and assess the risk of bias. RESULTS: Overall, 46 studies validating substance use/SUD (n = 46) measures were included in this review, in which 63% were conducted in clinical settings and 89% assessed the validity of SUD measures. Among the studies that assessed SUD screening measures, 78% examined a generic SUD measure, and the rest screened for specific disorders. Almost every study used a different survey measure. Overall, sensitivity and specificity tests were conducted in over a third of the studies for validation, and 10 studies used receiver operating characteristics curve. CONCLUSION: Findings suggest a lack of standardized methods in surveys measuring and reporting prevalence of substance use/SUD among US adults. It highlights a critical need to develop short measures for assessing SUD that do not require lengthy, time-consuming data collection that would be difficult to incorporate into population-based surveys assessing a multitude of health dimensions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022298280.

Inhibition of mRNA nuclear export promotes SARS-CoV-2 pathogenesis.

The nonstructural protein 1 (Nsp1) of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a virulence factor that targets multiple cellular pathways to inhibit host gene expression and antiviral response. However, the underlying mechanisms of the various Nsp1-mediated functions and their contributions to SARS-CoV-2 virulence remain unclear. Among the targets of Nsp1 is the mRNA (messenger ribonucleic acid) export receptor NXF1-NXT1, which mediates nuclear export of mRNAs from the nucleus to the cytoplasm. Based on Nsp1 crystal structure, we generated mutants on Nsp1 surfaces and identified an acidic N-terminal patch that is critical for interaction with NXF1-NXT1. Photoactivatable Nsp1 probe reveals the RNA Recognition Motif (RRM) domain of NXF1 as an Nsp1 N-terminal binding site. By mutating the Nsp1 N-terminal acidic patch, we identified a separation-of-function mutant of Nsp1 that retains its translation inhibitory function but substantially loses its interaction with NXF1 and reverts Nsp1-mediated mRNA export inhibition. We then generated a recombinant (r)SARS-CoV-2 mutant on the Nsp1 N-terminal acidic patch and found that this surface is key to promote NXF1 binding and inhibition of host mRNA nuclear export, viral replication, and pathogenicity in vivo. Thus, these findings provide a mechanistic understanding of Nsp1-mediated mRNA export inhibition and establish the importance of this pathway in the virulence of SARS-CoV-2.

Acute Pancreatitis Revealing a Diagnosis of Diffuse Large B-Cell Lymphoma.

Acute pancreatitis is a common gastroenterological condition that can occur due to several causes. While not required for diagnosis, imaging is often performed and may reveal unexpected findings such as pancreatic masses. Malignancies such as lymphoma are uncommon causes of acute pancreatitis, especially as the initial presentation of malignancy. We present a case of a young patient with acute pancreatitis caused by diffuse large B-cell lymphoma with extranodal disease secondarily involving the pancreas. Our case highlights the importance of keeping a broad differential for acute pancreatitis and considering rare etiologies such as pancreatic lymphoma in patients without another obvious culprit.

Daydreaming and grandiose delusions: development of the Qualities of Daydreaming Scale.

BACKGROUND: Daydreaming may contribute to the maintenance of grandiose delusions. Repeated, pleasant and vivid daydreams about the content of grandiose delusions may keep the ideas in mind, elaborate the details, and increase the degree of conviction in the delusion. Pleasant daydreams more generally could contribute to elevated mood, which may influence the delusion content. AIMS: We sought to develop a brief questionnaire, suitable for research and clinical practice, to assess daydreaming and test potential associations with grandiosity. METHOD: 798 patients with psychosis (375 with grandiose delusions) and 4518 non-clinical adults (1788 with high grandiosity) were recruited. Participants completed a daydreaming item pool and measures of grandiosity, time spent thinking about the grandiose belief, and grandiose belief conviction. Factor analysis was used to derive the Qualities of Daydreaming Scale (QuOD) and associations were tested using pairwise correlations and structural equation modelling. RESULTS: The questionnaire had three factors: realism, pleasantness, and frequency of daydreams. The measure was invariant across clinical and non-clinical groups. Internal consistency was good (alpha-ordinals: realism=0.86, pleasantness=0.93, frequency=0.82) as was test-retest reliability (intra-class coefficient=0.75). Daydreaming scores were higher in patients with grandiose delusions than in patients without grandiose delusions or in the non-clinical group. Daydreaming was significantly associated with grandiosity, time spent thinking about the grandiose delusion, and grandiose delusion conviction, explaining 19.1, 7.7 and 5.2% of the variance in the clinical group data, respectively. Similar associations were found in the non-clinical group. CONCLUSIONS: The process of daydreaming may be one target in psychological interventions for grandiose delusions.

Outcomes of Cold Snare Endoscopic Mucosal Resection of Nonampullary Duodenal Adenomas ≥1 cm: A Multicenter Study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) with use of electrocautery (conventional EMR) has historically been used to remove large duodenal adenomas, however, use of electrocautery can predispose to adverse events including delayed bleeding and perforation. Cold snare EMR (cs-EMR) has been shown to be safe and effective for removal of colon polyps, but data regarding its use in the duodenum is limited. The aim of this study is to evaluate the efficacy and safety of cs-EMR for nonampullary duodenal adenomas ≥1 cm. METHODS: This was a multicenter retrospective study of patients with nonampullary duodenal adenomas ≥1 cm who underwent cs-EMR between October 2014 and May 2023. Patients who received any form of thermal therapy were excluded. Primary outcomes were technical success and rate of recurrent adenoma. Secondary outcomes were adverse events and predictors of recurrence. RESULTS: A total of 125 patients underwent resection of 127 nonampullary duodenal adenomas with cs-EMR. Follow up data was available in 89 cases (70.1%). The recurrent adenoma rate was 31.5% (n=28). Adverse events occurred in 3.9% (n=5) with four cases of immediate bleeding (3.1%) and one case of delayed bleeding (0.8%). There were no cases of perforation. The presence of high-grade dysplasia was found to be an independent predictor of recurrence (OR: 10.9 [95% CI: 1.1-102.1], p=0.036). CONCLUSION: This retrospective multicenter study demonstrates that cs-EMR for nonampullary duodenal adenomas is safe and technically feasible with an acceptable recurrence rate. Future prospective studies are needed to directly compare outcomes of cs-EMR with conventional and underwater EMR.

TACTICS VR Stroke Telehealth Virtual Reality Training for Health Care Professionals Involved in Stroke Management at Telestroke Spoke Hospitals: Module Design and Implementation Study.

BACKGROUND: Stroke management in rural areas is more variable and there is less access to reperfusion therapies, when compared with metropolitan areas. Delays in treatment contribute to worse patient outcomes. To improve stroke management in rural areas, health districts are implementing telestroke networks. The New South Wales Telestroke Service provides neurologist-led telehealth to 23 rural spoke hospitals aiming to improve treatment delivery and patient outcomes. The training of clinical staff was identified as a critical aspect for the successful implementation of this service. Virtual reality (VR) training has not previously been used in this context. OBJECTIVE: We sought to develop an evidence-based VR training module specifically tailored for stroke telehealth. During implementation, we aimed to assess the feasibility of workplace deployment and collected feedback from spoke hospital staff involved in stroke management on training acceptability and usability as well as perceived training impact. METHODS: The TACTICS VR Stroke Telehealth application was developed with subject matter experts. During implementation, both quantitative and qualitative data were documented, including VR use and survey feedback. VR hardware was deployed to 23 rural hospitals, and use data were captured via automated Wi-Fi transfer. At 7 hospitals in a single local health district, staff using TACTICS VR were invited to complete surveys before and after training. RESULTS: TACTICS VR Stroke Telehealth was deployed to rural New South Wales hospitals starting on April 14, 2021. Through August 20, 2023, a total of 177 VR sessions were completed. Survey respondents (n=20) indicated a high level of acceptability, usability, and perceived training impact (eg, accuracy and knowledge transfer; mean scores 3.8-4.4; 5=strongly agree). Furthermore, respondents agreed that TACTICS VR increased confidence (13/18, 72%), improved understanding (16/18, 89%), and improved awareness (17/18, 94%) regarding stroke telehealth. A comparison of matched pre- and posttraining responses revealed that training improved the understanding of telehealth workflow practices (after training: mean 4.2, SD 0.6; before training: mean 3.2, SD 0.9; P<.001), knowledge on accessing stroke telehealth (mean 4.1, SD 0.6 vs mean 3.1, SD 1.0; P=.001), the awareness of stroke telehealth (mean 4.1, SD 0.6 vs mean 3.4, SD 0.9; P=.03), ability to optimally communicate with colleagues (mean 4.2, SD 0.6 vs mean 3.7, SD 0.9; P=.02), and ability to make improvements (mean 4.0, SD 0.6 vs mean 3.5, SD 0.9; P=.03). Remote training and deployment were feasible, and limited issues were identified, although uptake varied widely (0-66 sessions/site). CONCLUSIONS: TACTICS VR Stroke Telehealth is a new VR application specifically tailored for stroke telehealth workflow training at spoke hospitals. Training was considered acceptable, usable, and useful and had positive perceived training impacts in a real-world clinical implementation context. Additional work is required to optimize training uptake and integrate training into existing education pathways.

Primary Pancreatic Liposarcoma: An Unexpected Cause of a Pancreatic Mass.

Liposarcoma is the most common type of soft-tissue sarcoma and typically occurs in the extremities or retroperitoneum. Primary liposarcoma of the pancreas is exceedingly rare, with only 10 cases reported since 1979. We present a patient who was incidentally discovered to have a pancreatic mass on imaging, which was ultimately diagnosed as dedifferentiated pancreatic liposarcoma. We review the clinical and histologic features of pancreatic liposarcoma in this case and in the 10 previously reported cases to increase awareness and knowledge of this rare disease.

Cold snare endoscopic mucosal resection for colon polyps: a systematic review and meta-analysis.

BACKGROUND: Cold snare endoscopic mucosal resection (CS-EMR) can reduce the risks associated with electrocautery during colon polyp resection. Data on efficacy are variable. This systematic review and meta-analysis aimed to estimate the pooled efficacy and safety rates of CS-EMR. METHODS: We conducted a comprehensive literature search of multiple databases, from inception to March 2023, for studies addressing outcomes of CS-EMR for colon polyps. The weighted pooled estimates with 95 %CIs were calculated using the random effects model. I2 statistics were used to evaluate heterogeneity. RESULTS: 4137 articles were reviewed, and 16 studies, including 2592 polyps in 1922 patients (51.4 % female), were included. Overall, 54.4 % of polyps were adenomas, 45 % were sessile serrated lesions (SSLs), and 0.6 % were invasive carcinomas. Polyp recurrence after CS-EMR was 6.7 % (95 %CI 2.4 %-17.4 %, I2  = 94 %). The recurrence rate was 12.3 % (95 %CI 3.4 %-35.7 %, I2  = 94 %) for polyps ≥ 20 mm, 17.1 % (95 %CI 4.6 %-46.7 %, I2  = 93 %) for adenomas, and 5.7 % (95 %CI 3.2 %-9.9 %, I2  = 50 %) for SSLs. The pooled intraprocedural bleeding rate was 2.6 % (95 %CI 1.5 %-4.5 %, I2  = 51 %), the delayed bleeding rate was 1.5 % (95 %CI 0.8 %-2.7 %, I2  = 18 %), and no perforations or post-polypectomy syndromes were reported, with estimated rates of 0.6 % (95 %CI 0.3 %-1.3 %, I2  = 0 %) and 0.6 % (95 %CI 0.3 %-1.4 %, I2  = 0 %), respectively. CONCLUSION: CS-EMR demonstrated an excellent safety profile for colon polyps, with variable recurrence rates based on polyp size and histology. Large prospective studies are needed to validate these findings.

Influence of depression and interpersonal support on adherence to antiretroviral therapy among people living with HIV.

BACKGROUND: Poor adherence and under-utilization of antiretroviral therapy (ART) services have been major setbacks to achieving 95-95-95 policy goals in Sub-Saharan Africa. Social support and mental health challenges may serve as barriers to accessing and adhering to ART but are under-studied in low-income countries. The purpose of this study was to examine the association of interpersonal support and depression scores with adherence to ART among persons living with HIV (PLWH) in the Volta region of Ghana. METHODS: We conducted a cross-sectional survey among 181 PLWH 18 years or older who receive care at an ART clinic between November 2021 and March 2022. The questionnaire included a 6-item simplified ART adherence scale, the 20-item Center for Epidemiologic Studies Depression Scale (CES-D), and the 12-item Interpersonal Support Evaluation List-12 (ISEL-12). We first used a chi-squared or Fisher's exact test to assess the association between these and additional demographic variables with ART adherence status. We then built a stepwise multivariable logistic regression model to explain ART adherence. RESULTS: ART adherence was 34%. The threshold for depression was met by 23% of participants, but it was not significantly associated with adherence in multivariate analysis(p = 0.25). High social support was reported by 48.1%, and associated with adherence (p = 0.033, aOR = 3.45, 95% CI = 1.09-5.88). Other factors associated with adherence included in the multivariable model included not disclosing HIV status (p = 0.044, aOR = 2.17, 95% CI = 1.03-4.54) and not living in an urban area (p = 0.00037, aOR = 0.24, 95% CI = 0.11-0.52). CONCLUSION: Interpersonal support, rural residence, and not disclosing HIV status were independent predictors of adherence to ART in the study area.

Use of the endoscopic powered resection device for the management of scarred polyps.

Background and Aims: The endoscopic powered resection (EPR) device (EndoRotor, Interscope Inc, Northbridge, Mass, USA) is a novel nonthermal device that can be used for polyp and tissue removal in the GI tract. Here, we review the EPR device and illustrate its use for resection of scarred or fibrotic lesions in the GI tract. Methods: In this article and accompanying video, we describe the EPR device features, provide step-by-step instructions for device setup, and review case examples in which the EPR device was used for scarred polyp resection. We also review the current literature describing the use of the EPR device for scarred or challenging polyps. Results: Four lesions with scarring or fibrosis were successfully resected with the EPR device, either with the EPR device alone or as an adjunct to conventional resection methods. No adverse events occurred. A follow-up endoscopy was available in 1 case, which demonstrated no endoscopic or histologic evidence of residual or recurrent lesion. Conclusions: The endoscopic powered resection device can be used alone or as an adjunct to facilitate resection of lesions with significant fibrosis or scarring. This device serves as a useful addition to endoscopists' toolbox in the management of scarred lesions where other modalities might be technically challenging to use.