Immunotherapy-Induced Encephalitis: A Case of a Rare but Serious Complication of Anti-PD-1 Treatment

Son Linda Soy pictured.https://openworks.mdanderson.org/aprn-week-23/1023/thumbnail.jp

ATHENA: A Phase 3, Open-Label Study Of The Safety And Effectiveness Of Oliceridine (TRV130), A G-Protein Selective Agonist At The µ-Opioid Receptor, In Patients With Moderate To Severe Acute Pain Requiring Parenteral Opioid Therapy.

Background:Pain management with conventional opioids can be challenging due to dose-limiting adverse events (AEs), some of which may be related to the simultaneous activation of β-arrestin (a signaling pathway associated with opioid-related AEs) and G-protein pathways. The investigational analgesic oliceridine is a G-protein-selective agonist at the µ-opioid receptor with less recruitment of β-arrestin. The objective of this phase 3, open-label, multi-center study was to evaluate the safety and tolerability, of IV oliceridine for moderate to severe acute pain in a broad, real-world patient population, including postoperative surgical patients and non-surgical patients with painful medical conditions. Methods:Adult patients with a score ≥4 on 11-point NRS for pain intensity received IV oliceridine either by bolus or PCA; multimodal analgesia was permitted. Safety was assessed using AE reports, study discontinuations, clinical laboratory and vital sign measures. Results:A total of 768 patients received oliceridine. The mean age (SD) was 54.1 (16.1) years, with 32% ≥65 years of age. Most patients were female (65%) and Caucasian (78%). Surgical patients comprised the majority of the study population (94%), most common being orthopedic (30%), colorectal (15%) or gynecologic (15%) procedures. Multimodal analgesia was administered to 84% of patients. Oliceridine provided a rapid reduction in NRS pain score by 2.2 ± 2.3 at 30 mins from a score of 6.3 ± 2.1 (at baseline) which was maintained to the end of treatment. No deaths or significant cardiorespiratory events were reported. The incidence of AEs leading to early discontinuation and serious AEs were 2% and 3%, respectively. Nausea (31%), constipation (11%), and vomiting (10%) were the most common AEs. AEs were mostly of mild (37%) or moderate (25%) severity and considered possibly or probably related to oliceridine in 33% of patients. Conclusion:Oliceridine IV for the management of moderate to severe acute pain was generally safe and well tolerated in the patients studied. ClinicalTrialsgov identifier:NCT02656875

A Survey on Detection of LLMs-Generated Content

The burgeoning capabilities of advanced large language models (LLMs) such as ChatGPT have led to an increase in synthetic content generation with implications across a variety of sectors, including media, cybersecurity, public discourse, and education. As such, the ability to detect LLMs-generated content has become of paramount importance. We aim to provide a detailed overview of existing detection strategies and benchmarks, scrutinizing their differences and identifying key challenges and prospects in the field, advocating for more adaptable and robust models to enhance detection accuracy. We also posit the necessity for a multi-faceted approach to defend against various attacks to counter the rapidly advancing capabilities of LLMs. To the best of our knowledge, this work is the first comprehensive survey on the detection in the era of LLMs. We hope it will provide a broad understanding of the current landscape of LLMs-generated content detection, offering a guiding reference for researchers and practitioners striving to uphold the integrity of digital information in an era increasingly dominated by synthetic content. The relevant papers are summarized and will be consistently updated at https://github.com/Xianjun-Yang/Awesome_papers_on_LLMs_detection.git.Comment: We will keep updating at https://github.com/Xianjun-Yang/Awesome_papers_on_LLMs_detection.gi

The association between socioeconomic status and disability after stroke: Findings from the Adherence eValuation After Ischemic stroke Longitudinal (AVAIL) registry

Background Stroke is the leading cause of disability among adults in the United States. The association of patients’ pre-event socioeconomic status (SES) with post-stroke disability is not well understood. We examined the association of three indicators of SES—educational attainment, working status, and perceived adequacy of household income—with disability 3-months following an acute ischemic stroke. Methods We conducted retrospective analyses of a prospective cohort of 1965 ischemic stroke patients who survived to 3 months in the Adherence eValuation After Ischemic stroke – Longitudinal (AVAIL) study. Multivariable logistic regression was used to examine the relationship of level of education, pre-stroke work status, and perceived adequacy of household income with disability (defined as a modified Rankin Scale of 3–5 indicating activities of daily living limitations or constant care required). Results Overall, 58% of AVAIL stroke patients had a high school or less education, 61% were not working, and 27% perceived their household income as inadequate prior to their stroke. Thirty five percent of patients were disabled at 3-months. After adjusting for demographic and clinical factors, stroke survivors who were unemployed or homemakers, disabled and not-working, retired, less educated, or reported to have inadequate income prior to their stroke had a significantly higher odds of post-stroke disability. Conclusions In this cohort of stroke survivors, socioeconomic status was associated with disability following acute ischemic stroke. The results may have implications for public health and health service interventions targeting stroke survivors at risk of poor outcomes

Remotely-sensed imagery vs. eye-level photography: Evaluating associations among measurements of tree cover density

AbstractThe easy availability and widespread use of remotely-sensed imagery, especially Google Earth satellite imagery, makes it simple for urban forestry professionals to assess a site and measure tree cover density without visiting the site. Remotely-sensed tree cover density has become the dominant criterion for urban forestry regulations in many countries, but it is unclear how much such measures match the eye-level tree cover density that people experience; or the information gained through site visits, eye-level photography, or from consulting with citizens. To address this uncertainty, we assessed associations among two remotely-sensed and three eye-level tree cover density measures for 140 community street sites across the Midwestern United States with low, medium, or high tree cover coverage by using linear regression analysis. We found significant associations among the two remotely-sensed measures and the three eye-level measures across the three levels of tree cover. The associations between any pair of remotely-sensed and eye-level measures, however, diminish dramatically as canopy cover increased. At high levels of canopy cover, all associations between the remotely-sensed measures and the eye-level measures became statistically insignificant. These findings suggest that measures from remotely-sensed imagery fail to represent the amount of tree cover people perceive at eye-level when canopy cover is medium or high at the site scale. Therefore, the current urban forestry planning regulations, which rely heavily on remotely-sensed tree cover density measurements, need to be revised. We suggest strategic spots where eye-level measures of tree cover density should be emphasized

Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model

Treatment of large segmental bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials. This project was designed to rapidly assess and compare promising biodegradable osteoconductive scaffolds for use in the systematic development of new bone regeneration methodologies that combine scaffolds, sources of osteogenic cells, and bioactive scaffold modifications. Promising biomaterials and scaffold fabrication methods were identified in laboratories at Rutgers, MIT, Integra Life Sciences, and Mayo Clinic. Scaffolds were fabricated from various materials, including poly(L-lactide-co-glycolide) (PLGA), poly(L-lactide-co-ɛ-caprolactone) (PLCL), tyrosine-derived polycarbonate (TyrPC), and poly(propylene fumarate) (PPF). Highly porous three-dimensional (3D) scaffolds were fabricated by 3D printing, laser stereolithography, or solvent casting followed by porogen leaching. The canine femoral multi-defect model was used to systematically compare scaffold performance and enable selection of the most promising substrate(s) on which to add cell sourcing options and bioactive surface modifications. Mineralized cancellous allograft (MCA) was used to provide a comparative reference to the current clinical standard for osteoconductive scaffolds. Percent bone volume within the defect was assessed 4 weeks after implantation using both MicroCT and limited histomorphometry. Bone formed at the periphery of all scaffolds with varying levels of radial ingrowth. MCA produced a rapid and advanced stage of bone formation and remodeling throughout the defect in 4 weeks, greatly exceeding the performance of all polymer scaffolds. Two scaffold constructs, TyrPC[subscript PL]/TCP and PPF4[subscript SLA]/HA[subscript PLGA Dip], proved to be significantly better than alternative PLGA and PLCL scaffolds, justifying further development. MCA remains the current standard for osteoconductive scaffolds.United States. Army Medical Research and Materiel Command (Armed Forces Institute of Regenerative Medicine)United States. Office of Naval ResearchUnited States. Air Force. Office of the Surgeon GeneralUnited States. NavyNational Institutes of Health (U.S.)United States. Veterans AdministrationCleveland Clinic Foundatio

SARS-CoV-2 breakthrough infections after COVID-19 vaccination in patients with inflammatory bowel disease:a systematic review and meta-analysis

Background: Patients with inflammatory bowel disease (IBD) have an attenuated serologic response to COVID-19 vaccination. It is unclear whether an impaired immune response in vaccinated IBD patients impacts the susceptibility to SARS-CoV-2 infection and occurrence of severe COVID-19. Objectives:To evaluate SARS-CoV-2 breakthrough infection rates and the disease course of COVID-19 in vaccinated IBD patients. Design: A systematic literature search and meta-analysis was performed. Data sources and methods: The search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and CINAHIL. The articles were independently screened and selected by two reviewers. A random-effects model was used to calculate the pooled relative risk for breakthrough infections in vaccinated IBD patients and controls. Results: A total of 16 studies were included, with study periods ranging from January 2020 to October 2021 and follow-up time from 3 weeks to 6 months. The breakthrough infection rates range from 0 to 37.4% in vaccinated IBD patients. The disease course of COVID-19 was generally mild, with low hospitalization and mortality rates (0–8.7% and 0–4.3%, respectively). Vaccinated IBD patients had a significantly lower relative risk of breakthrough infection rate compared to unvaccinated controls (risk ratio: 0.07, 95% CI: 0.03–0.18). No difference was observed between IBD patients and non-IBD controls, and between partially and fully vaccinated IBD patients. The impact of immunosuppressive therapy on breakthrough infection rates differs between studies. Most studies showed no impact from immunosuppressive treatment, anti-tumour necrosis factor alpha or corticosteroids and other biologics; one study reported higher rates for patients treated with infliximab versus vedolizumab. Conclusion: Vaccination is effective to prevent COVID-19 infections in patients with IBD. Breakthrough infections do occur, but the disease course is generally mild. Available data seem to suggest a declining trend of breakthrough infections during calendar time. Registration: The protocol was published in the PROSPERO database (CRD42021292853).</p