Acceptance of SARS-CoV-2 Surveillance Testing Among Patients Receiving Dialysis: A Cluster Randomized Trial.

Importance: Integrating routine SARS-CoV-2 testing in dialysis facilities may benefit patients receiving dialysis by mitigating risks of serious illness and reducing transmission. Patient acceptance of nonmandatory testing is unknown. Objective: To evaluate the acceptance of 2 SARS-CoV-2 testing strategies among patients in hemodialysis facilities nationwide. Design, Setting, and Participants: This nationwide cluster (dialysis facility-level) randomized trial investigated the acceptance of SARS-CoV-2 testing among patients receiving maintenance hemodialysis at facilities located in 22 states. Intervention: Anterior nares real-time reverse transcriptase-polymerase chain reaction tests offered once every 2 weeks (static testing facilities) vs offered once a week, once every 2 weeks, or once a month depending on county COVID-19 infection prevalence (dynamic testing facilities). Facilities were randomized by county, and tests were offered for 3 months between February 4 and July 24, 2023. Main Outcomes and Measures: The primary outcome was test acceptance. Secondary outcomes included the proportion of patients who accepted at least 1 test. Results: In total, 62 hemodialysis facilities were randomized and 57 participated. Among 2389 participating patients, the median age was 64 (IQR, 54-74) years, 1341 (56%) were male, 138 (6%) were categorized as American Indian, 60 (3%) Asian, 885 (37%) Black, 75 (3%) Native Hawaiian or Pacific Islander, 338 (14%) Hispanic, and 876 (37%) White; and 1603 (67%) had diabetes. A median of 6 (IQR, 6-6) tests were offered per patient in the static arm and 4 (3-6) tests in the dynamic arm. Test acceptance was low: 8% of offered tests were accepted in each of the test arms. Among 503 patients who accepted at least 1 test, the median percentage of offered tests that were accepted was 16% (IQR, 17%-42%) using the static testing strategy and 50% (IQR, 33%-75%) using the dynamic testing strategy (P < .001). Older patients (odds ratio [OR], 1.08 [95% CI, 1.01-1.16] per 5-year age increment), patients with (vs without) diabetes (OR, 1.59 [95% CI, 1.18-2.16]), and women compared with men (OR, 1.30 [95% CI, 0.98-1.73]) were more likely to accept multiple tests. Patients designated in the electronic health record as Hispanic were more likely than patients designated as White (OR, 1.78 [95% CI, 1.15-2.76]) to accept at least 1 test, whereas patients living in zip codes electing Republican representatives to Congress were less likely than patients living in zip codes electing Democratic representatives (OR, 0.34 [95% CI, 0.17-0.69]) to accept multiple tests. Conclusions and Relevance: In this cluster randomized trial evaluating 2 SARS-CoV-2 testing strategies in dialysis facilities, test acceptance was low, and a dynamic testing strategy anchored to COVID-19 infection prevalence did not outperform a static testing strategy of every 2 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT05225298.

Cold Snare Resection in the Colorectum: When to Choose it, When to Avoid it, and How to Do it.

Cold snaring is now the preferred resection method for the majority of colorectal polyps encountered during colonoscopy. A key advantage of cold resection over resection utilizing electrocautery is a substantially lower risk of delayed hemorrhage. Cold snare resection is preferred for all lesions ≤ 10 mm and for non-dysplastic sessile serrated lesions of any size, but should be avoided when lesions have a significant risk of submucosal invasion or fibrosis. Cold snare resection can be considered for certain lesions 11-19 mm in size and some lateral spreading lesions ≥ 20 mm. This review discusses tips and techniques to optimize cold snare resection.

MERTK inhibition selectively activates a DC - T-cell axis to provide anti-leukemia immunity.

TAM-family tyrosine kinases (TYRO3, AXL and MERTK) are potential cancer therapeutic targets. In previous studies MERTK inhibition in the immune microenvironment was therapeutically effective in a B-cell acute leukemia (B-ALL) model. Here, we probed anti-leukemia immune mechanisms and evaluated roles for TYRO3 and AXL in the leukemia microenvironment. Host Mertk knock-out or MERTK inhibitor MRX-2843 increased CD8α+ dendritic cells (DCs) with enhanced antigen-presentation capacity in the leukemia microenvironment and inhibited leukemogenesis. High MERTK or low DC gene expression were associated with poor prognosis in pediatric ALL patients, indicating the clinical relevance of these findings. MRX-2843 increased CD8+ T-cell numbers and prevented induction of exhaustion markers, implicating a DC - T-cell axis. Indeed, combined depletion of CD8α+ DCs and CD8+ T-cells was required to abrogate anti-leukemia immunity in Mertk-/- mice. Tyro3-/- mice were also protected against B-ALL, implicating TYRO3 as an immunotherapeutic target. In contrast to Mertk-/- mice, Tyro3-/- did not increase CD8α+ DCs with enhanced antigen-presentation capacity and therapeutic activity was less dependent on DCs, indicating a different immune mechanism. Axl-/- did not impact leukemogenesis. These data demonstrate differential TAM kinase roles in the leukemia microenvironment and provide rationale for development of MERTK and/or TYRO3-targeted immunotherapies.

The Critical Social Processes for Standardising the Ecological Monitoring of Australian Landscapes.

For a long time, ecological monitoring across Australia has utilised a wide variety of different methodologies resulting in data that is difficult to analyse across place or time. In response to these limitations, a new systematic approach to ecological monitoring has been developed in collaboration between the Terrestrial Ecosystem Research Network and the Australian Department of Climate Change, Energy, the Environment and Water - the Ecological Monitoring System Australia (EMSA). A qualitative approach involving focus groups and semi-structured interviews was undertaken to review perceptions of the introduction of the EMSA protocols amongst Natural Resource Management practitioners and other key stakeholders. We found that environmental management stakeholders recognise there will be many advantages from the standardisation of ecological monitoring. However, key concerns emerged regarding the capacity needed to implement the standard protocols, the utility of the resultant data for regional projects, and the scope for adaptive co-management under the EMSA. Stakeholders emphasised the need for autonomy and flexibility, so their participation in protocol development can facilitate regional adoption of the standards. Respondents' concerns about a perceived lack of genuine consultation and acknowledgement of feedback revealed the importance of clear communication at all stages of an environmental management project aiming to standardise practices. Our findings indicate that reflexivity will be vital to address the complexity involved in standardisation of ecological monitoring. Formal processes of social learning will need to be integrated into environmental management approaches to account for the increasing complexity of socio-ecological systems as they are challenged by global change.

Differential diagnosis of suspected multiple sclerosis: global health considerations.

The differential diagnosis of multiple sclerosis can present specific challenges in patients from Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific. In these areas, environmental factors, genetic background, and access to medical care can differ substantially from those in North America and western Europe, where multiple sclerosis is most common. Furthermore, multiple sclerosis diagnostic criteria have been developed primarily using data from North America and western Europe. Although some diagnoses mistaken for multiple sclerosis are common regardless of location, a comprehensive approach to the differential diagnosis of multiple sclerosis in Latin America, Africa, the Middle East, eastern Europe, southeast Asia, and the Western Pacific regions requires special consideration of diseases that are prevalent in those locations. A collaborative effort has therefore assessed global differences in multiple sclerosis differential diagnoses and proposed recommendations for evaluating patients with suspected multiple sclerosis in regions beyond North America and western Europe.

Editors' Note: 2024 Annual Report Regarding JAACAP's Antiracist Journey.

In 2020, we wrote to you about our dedication and vision for JAACAP "to be antiracist at every level."1 Over the last 4 years we have pursued initiatives "to reshape the Journal to pursue this vision."2-4 In this article, we provide an update on these goals and initiatives (Figure 1). These initiatives include both scientific journals in the JAACAP family, JAACAP and JAACAP Open. Through this work we aspire to be a leader among mental health journals in our intentional pursuit of antiracist policies and practices.

Computer-aided diagnosis for the resect-and-discard strategy for colorectal polyps: a systematic review and meta-analysis.

BACKGROUND: The resect-and-discard strategy allows endoscopists to replace post-polypectomy pathology with real-time prediction of polyp histology during colonoscopy (optical diagnosis). We aimed to investigate the benefits and harms of implementing computer-aided diagnosis (CADx) for polyp pathology into the resect-and-discard strategy. METHODS: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and Scopus from database inception to June 5, 2024, without language restrictions, for diagnostic accuracy studies that assessed the performance of real-time CADx systems, compared with histology, for the optical diagnosis of diminutive polyps (≤5 mm) in the entire colon. We synthesised data for three strategies: CADx-alone, CADx-unassisted, and CADx-assisted; when the endoscopist was involved in the optical diagnosis, we synthesised data exclusively from diagnoses for which confidence in the prediction was reported as high. The primary outcomes were the proportion of polyps that would have avoided pathological assessment (ie, the proportion optically diagnosed with high confidence; main benefit) and the proportion of polyps incorrectly predicted due to false positives and false negatives (main harm), directly compared between CADx-assisted and CADx-unassisted strategies. We used DerSimonian and Laird's random-effects model to calculate all outcomes. We used Higgins I2 to assess heterogeneity, the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate certainty, and funnel plots and Egger's test to examine publication bias. This study is registered with PROSPERO, CRD42024508440. FINDINGS: We found 1019 studies, of which 11 (7400 diminutive polyps, 3769 patients, and 185 endoscopists) were included in the final meta-analysis. Three studies (1817 patients and 4086 polyps [2148 neoplastic and 1938 non-neoplastic]) provided data to directly compare the primary outcome measures between the CADx-unassisted and CADx-assisted strategies. We found no significant difference between the CADx-assisted and CADx-unassisted strategies for the proportion of polyps that would have avoided pathological assessment (90% [88-93], 3653 [89·4%] of 4086 polyps diagnosed with high confidence vs 90% [95% CI 85-94], 3588 [87·8%] of 4086 polyps diagnosed with high confidence; risk ratio 1·01 [95% CI 0·99-1·04; I2=53·49%; low-certainty evidence; Egger's test p=0·18). The proportion of incorrectly predicted polyps was lower with the CADx-assisted strategy than with the CADx-unassisted strategy (12% [95% CI 7-17], 523 [14·3%] of 3653 polyps incorrectly predicted with a CADx-assisted strategy vs 13% [6-20], 582 [16·2%] of 3588 polyps incorrectly diagnosed with a CADx-unassisted strategy; risk ratio 0·88 [95% CI 0·79-0·98]; I2=0·00%; low-certainty evidence; Egger's test p=0·18). INTERPRETATION: CADx did not produce benefit nor harm for the resect-and-discard strategy, questioning its value in clinical practice. Improving the accuracy and explainability of CADx is desired. FUNDING: European Commission (Horizon Europe), the Japan Society of Promotion of Science, and Associazione Italiana per la Ricerca sul Cancro.

Still "Don't Ask" more than a decade later: The impact of research barriers for LGB+ military couples.

Despite the repeal of "Don't Ask, Don't Tell" (DADT) over a decade ago, military processes and policies continue to function as significant structural and institutional barriers to research aimed at optimizing resources for military couples and families with marginalized sexual identities. Such research is essential given the apparent mental health and related disparities among lesbian, gay, bisexual, and those with other marginalized sexual identities (LGB+) active-duty service members (SMs), as well as the absence of appropriately tailored resources to support these members of the military community. In this paper, we review the empirical literature on the experiences and psychological health of LGB+ military couples, revealing severe limitations in our understanding of these diverse military romantic partnerships. We illuminate process-related barriers to conducting this essential research through an illustrative case example. Our review concludes with specific recommendations for reform and advocacy distinguished by coordinated efforts inclusive of all five military branches, policymakers, military leaders, researchers, and LGB+ stakeholders.

Risk factors for inadequate bowel preparation in colonoscopy: a comprehensive systematic review and meta-analysis.

INTRODUCTION: Inadequate bowel preparation (IBP) prior to colonoscopy remains a common problem. This meta-analysis aimed to assess the risk factors associated with IBP. METHODS: We searched multiple databases for studies that assessed risk factors for IBP after adjustment and reported the data as adjusted odds ratios (OR) with 95% confidence intervals. Meta-analyses were conducted using a random-effects model, and pooled adjusted ORs for risk factors reported in ≥3 studies were constructed. RESULTS: 154 studies with 258,257 participants were included. We analyzed 48 unique risk factors. Sociodemographic predictors of IBP were Medicaid insurance, obesity, current tobacco use, age≥65, Black race, low education level, male gender, and unmarried status. Comorbidity-related predictors of IBP were any psychiatric disease, cirrhosis, ASA class≥3, poor functional status, constipation, diabetes, prior abdominopelvic surgery, and hematochezia. Medication-related predictors of IBP were tricyclic antidepressants (TCA), antidepressants, opioid, non-TCA antidepressants, and calcium channel blockers. Preparation/procedure-related predictors of IBP were brown liquid rectal effluent, any incomplete bowel preparation (BP) intake, lack of split-dose BP, increased BP-to-defecation interval, any non-adherence to dietary instructions, increased BP-to-colonoscopy interval, any BP intolerance, prior IBP, and inpatient status. While afternoon colonoscopy was a predictor of IBP, subgroup analysis of prospective studies revealed no significant association. CONCLUSIONS: Our meta-analysis focused on adjusted risk factors to provide precise estimates of the most important risk factors for IBP. Our findings could help develop a validated prediction model to identify high-risk patients for IBP, improve colonoscopy outcomes, reduce the need for repeat colonoscopies, and reduce associated healthcare costs.

Performance of bowel preparation quality scales in patients with Crohn's disease.

BACKGROUND: The performance of bowel preparation (BP) in patients with Crohn's disease (CD) is unknown. AIMS: To evaluate the operating properties of instruments used to assess BP quality in patients with CD. METHODS: We used the Boston Bowel Preparation Scale, modified Boston Bowel Preparation Scale, Harefield Cleansing Scale, Food and Drug Administration Bowel Cleansing Assessment Scale (BCAS), and a 100-mm visual analogue scale of bowel cleanliness to assess BP quality in 50 videos from 40 patients with CD. We assessed endoscopic activity with the Simple Endoscopic Score for CD (SES-CD). Assessments were on endoscope insertion and withdrawal. Reliability was quantified using the intraclass correlation coefficient (ICC). We assessed validity by within-patient correlation between instruments and the visual analogue scale using mixed-effect models. The correlation between BP quality and SES-SD scores was assessed using Spearman's rho. RESULTS: Inter- and intra-rater reliability for all BP quality instruments was substantial (ICC ≥0.61) except for the Food and Drug Administration BCAS on insertion (inter-rater reliability ICC ≥0.41). The visual analogue scale had substantial inter- and almost perfect (ICC ≥0.81) intra-rater reliability. Correlation coefficients for the validity of the instruments exceeded 0.58. BP quality and endoscopic disease activity scores in the colon were negatively correlated. CONCLUSION: Most existing instruments reliably assess BP quality in patients with CD. These results support the use of these instruments in clinical practice, provide a framework for scoring BP quality in CD clinical trials, and support evaluation of novel BP agents in patients with CD.

The Importance of Digital Lung Tomosynthesis in Overcoming Computed-Tomography-to-Body Divergence During Bronchoscopic Biopsies of Peripheral Lung Nodules.

The advent of robotic bronchoscopy coupled with electromagnetic navigation bronchoscopy (EMN) and shape-sensing technology have increased diagnostic yields for peripheral pulmonary nodules compared to traditional bronchoscopy. Yet, diagnostic yields from these bronchoscopic platforms still fall short of where they should be. This shortfall is in large part due to a lack of advanced imaging during peripheral bronchoscopy and computed tomography (CT)-to-body divergence (CTBD). Digital lung tomosynthesis (DLT) is an advanced imaging modality that helps overcome CTBD during bronchoscopic biopsies of lung nodules. DLT is a quasi-3D imaging technique, which reconstructs tomographic images of the lung from a series of 2D fluoroscopic projection images. These images can be acquired either using a digital flat panel fluoroscopy machine or a fluoroscopy machine with a more traditional image-intensifier present in most standard bronchoscopy suites. This review aims to explain the mechanisms of both CTBD and DLT to help diagnose early-stage lung cancer more effectively.

Embedded-deep-learning-based sample-to-answer device for on-site malaria diagnosis.

Improvements in digital microscopy are critical for the development of a malaria diagnosis method that is accurate at the cellular level and exhibits satisfactory clinical performance. Digital microscopy can be enhanced by improving deep learning algorithms and achieving consistent staining results. In this study, a novel miLab™ device incorporating the solid hydrogel staining method was proposed for consistent blood film preparation, eliminating the use of complex equipment and liquid reagent maintenance. The miLab™ ensures consistent, high-quality, and reproducible blood films across various hematocrits by leveraging deformable staining patches. Embedded-deep-learning-enabled miLab™ was utilized to detect and classify malarial parasites from autofocused images of stained blood cells using an internal optical system. The results of this method were consistent with manual microscopy images. This method not only minimizes human error but also facilitates remote assistance and review by experts through digital image transmission. This method can set a new paradigm for on-site malaria diagnosis. The miLab™ algorithm for malaria detection achieved a total accuracy of 98.86% for infected red blood cell (RBC) classification. Clinical validation performed in Malawi demonstrated an overall percent agreement of 92.21%. Based on these results, miLab™ can become a reliable and efficient tool for decentralized malaria diagnosis.

MERTK Is a Potential Therapeutic Target in Ewing Sarcoma.

Outcomes are poor in patients with advanced or relapsed Ewing sarcoma (EWS) and current treatments have significant short- and long-term side effects. New, less toxic and more effective treatments are urgently needed. MER proto-oncogene tyrosine kinase (MERTK) promotes tumor cell survival, metastasis, and resistance to cytotoxic and targeted therapies in a variety of cancers. MERTK was ubiquitously expressed in five EWS cell lines and five patient samples. Moreover, data from CRISPR-based library screens indicated that EWS cell lines are particularly dependent on MERTK. Treatment with MRX-2843, a first-in-class, MERTK-selective tyrosine kinase inhibitor currently in clinical trials, decreased the phosphorylation of MERTK and downstream signaling in a dose-dependent manner in A673 and TC106 cells and provided potent anti-tumor activity against all five EWS cell lines, with IC50 values ranging from 178 to 297 nM. Inhibition of MERTK correlated with anti-tumor activity, suggesting MERTK inhibition as a therapeutic mechanism of MRX-2843. Combined treatment with MRX-2843 and BCL-2 inhibitors venetoclax or navitoclax provided enhanced therapeutic activity compared to single agents. These data highlight MERTK as a promising therapeutic target in EWS and provide rationale for the development of MRX-2843 for the treatment of EWS, especially in combination with BCL-2 inhibitors.

Distal cap-assisted EMR allows the safe and effective resection of adherent dysplastic lesions in the setting of inflammatory bowel disease: a multicenter retrospective study (with video).

BACKGROUND AND AIMS: EMR is established as the primary approach for large and complex dysplastic lesions. However, submucosal fibrosis caused by previous attempts at removal, biopsy sampling, inflammation, or tattoo placement can cause a benign "negative lift sign" and create difficulty for EMR. Here, we present the use of distal cap-assisted EMR (EMR-DC) specifically for the use of resecting dysplastic colonic lesions when submucosal fibrosis is present in patients with inflammatory bowel disease (IBD). METHODS: Sixteen IBD patients were retrospectively evaluated from 2 high-volume centers. Patient demographics, lesion pathology and classification, outcomes including time and success of resection, serious adverse events (SAEs) within 30 days of the procedure, and efficacy were measured. RESULTS: Seventy-five percent of patients treated with EMR-DC achieved complete resection with no SAEs within 30 days of the procedure. CONCLUSIONS: EMR-DC represents an attractive option for the resection of adherent, dysplastic lesions in chronic IBD that is effective, safe, and inexpensive.