Corrigendum: Regulatory T cells targeting a pathogenic MHC class II: insulin peptide epitope postpone spontaneous autoimmune diabetes.

[This corrects the article DOI: 10.3389/fimmu.2023.1207108.].

Left atrial myxoma with cardiogenic shock following a myocardial infarction: a case report.

BACKGROUND: Myxomas are the most common primary cardiac tumor and typically originate in the left atrium. Atrial myxomas may present following complications of obstruction and emboli. If an atrial myxoma goes untreated, complications such as congestive heart failure, embolic stroke, and sudden death can occur. CASE PRESENTATION: A 58-year-old Caucasian male presented following a cardiac arrest. He was taken emergently to the cardiac catheterization lab and received two drug eluting stents. Following the procedure, he was found to have a left atrial mass that was intermittently obstructing the mitral valve on echocardiography. After leaving the cardiac catheterization lab, he was hypotensive and placed on multiple intravenous medications for hemodynamic support as well as an Impella device. Following medical optimization, he underwent one vessel coronary artery bypass graft as well as surgical excision of the left atrial mass, which pathology had shown to be an atrial myxoma. CONCLUSION: This patient's case of cardiogenic shock following revascularization was complicated by the identification of an atrial myxoma, which, when large enough, can obstruct blood flow through the mitral valve leading to acute mitral dynamic stenosis. This condition results in circulatory collapse due to obstruction of the left ventricle in diastole as the myxoma occludes the mitral valve.

Identifying contributing factors and locations of pedestrian severe crashes using hazard-based duration model.

Pedestrian safety remains a significant concern, with the growing number of severe pedestrian crashes resulting in substantial human and economic costs. Previous research into pedestrian crashes has extensively analyzed the influences of weather, lighting, and pedestrian demographics. However, these studies often overlook the critical spatial variables that contribute to pedestrian crashes. Our study aims to explore these overlooked spatial variables by examining the distance pedestrians travel before encountering a severe crash. This approach provides a supplementary perspective in safety analysis, emphasizing the importance of pedestrian movement patterns. The model considers various factors that may influence pedestrian traveled distance before being involved in a severe crash, such as weather conditions, lighting conditions, and pedestrian demographics. Ohio's pedestrian-involved crashes were gathered and analyzed as a case study. The results indicated that 50 % of fatal pedestrian crashes occurred within 0.84 miles of the pedestrians' residences. Moreover, it was shown that factors including lighting condition, pedestrian age, drug toxication, and the location at impact significantly influence the pedestrians traveled distance. These findings provide valuable insights into the spatial distribution of pedestrian crashes and shed light on the factors contributing to their severity. By understanding these relationships, policymakers and urban planners can design targeted interventions such as improving street lighting, implementing traffic calming measures, and developing safety awareness campaigns for specific age groups, to enhance pedestrian safety and reduce the incidence of severe crashes.

A framework for proactive safety evaluation of intersection using surrogate safety measures and non-compliance behavior.

In recent years, identifying road users' behavior and conflicts at intersections have become an essential data source for evaluating traffic safety. According to the Federal Highway Administration (FHWA), in 2020, more than 50% of fatal and injury crashes occurred at or near intersections, necessitating further investigation. This study developed an innovative artificial intelligence (AI)-based video analytic tool to assess intersection safety using surrogate safety measures and non-compliance behavior. To extract the trajectory data, a real-time AI detection model - YOLO-v5 with a tracking framework based on the DeepSORT algorithm was deployed. 54 h of high-resolution video data were collected at six signalized intersections (including three 3-leg and three 4-leg intersections) in Glassboro, New Jersey. Non-compliance behaviors, such as redlight running and pedestrian crossing outside the crosswalk, are captured to better understand the risky behaviors at these locations. The proposed approach achieved an accuracy of 92% to 98% for detecting and tracking road users' trajectories. Additionally, the developed tool also provided directional traffic volumes, pedestrian volumes, vehicles running a red light, pedestrian crossing outside the crosswalk events, and PET and TTC for crossing conflicts between vehicles. Furthermore, an extreme value theory (EVT) was used to estimate the number of crashes at each intersection utilizing the frequency of PETs and TTCs. Finally, the intersections were ranked based on the calculated score considering the severity of crashes. Overall, the developed tool and the crash estimation, as well as the model and ranking method, can provide valuable information for engineers and policymakers to assess the safety of intersections and implement effective countermeasures to mitigate intersection-involved crashes.

Association between Pharmacists' Country of Qualifying Education and Practising in a Hospital Setting: A Cross-Sectional Ontario Study.

Background: It is hypothesized that international pharmacy graduates (IPGs) are underrepresented in more clinically challenging work. Objective: To examine the association between country of qualifying education for pharmacists in Ontario and the likelihood of practising in a hospital setting. Methods: This study was based on publicly available data from the Ontario College of Pharmacists website, specifically records for all Ontario pharmacists with authorization to provide patient care and for whom country of qualifying education and an accredited pharmacy as a place of practice were reported. Pharmacists who met the inclusion criteria were categorized as Canadian graduates or IPGs. The odds ratio (OR) and 95% confidence interval (CI) for reporting hospital pharmacy as a place of practice were estimated by fitting a logistic regression, with adjustment for gender and years since graduation. Results: A total of 14 689 pharmacists were included in the study: 7403 (50.4%) Canadian graduates and 7286 (49.6%) IPGs. These pharmacists worked in a total of 5028 accredited pharmacies (243 hospital pharmacies [4.8%] and 4785 community pharmacies [95.2%]). Among Canadian graduates, 2458 (33.2%) reported at least 1 hospital pharmacy practice site, whereas the proportion was much smaller among IPGs (427, 5.9%). Canadian graduates represented 85.2% (2458/2885) of all pharmacists who reported hospital practice. The estimated crude OR for practice in a hospital pharmacy was 7.98 (95% CI 7.16-8.91), and the adjusted OR was 7.12 (95% CI 6.39-7.98). Conclusions: IPGs may face barriers impeding their ability to practise in a hospital setting. Providing opportunities such as structured clinical training and experiential placements may facilitate integration of IPGs in institutional settings.

Contexte: On émet l'hypothèse que les diplômés internationaux en pharmacie (DIP) sont sous-représentés dans des tâches plus cliniquement exigeantes. Objectif: Étudier l'association entre le pays de formation qualifiante des pharmaciens en Ontario et la probabilité de pratiquer dans un environnement hospitalier. Méthodes: Cette étude se fondait sur des données accessibles au public sur le site Web de l'Ordre des pharmaciens de l'Ontario, plus précisément les dossiers de tous les pharmaciens de l'Ontario autorisés à prodiguer des soins aux patients et pour lesquels le pays de formation qualifiante ainsi qu'une pharmacie accréditée en tant que lieu de pratique étaient signalés. Les pharmaciens répondant aux critères d'inclusion ont été catégorisés en tant que diplômés canadiens ou DIP. Le rapport de cotes (RC) et l'intervalle de confiance (IC) à 95 % pour le signalement de la pharmacie pratiquée en milieu hospitalier ont été estimés en utilisant une régression logistique, tenant compte du sexe et du nombre d'années depuis l'obtention du diplôme. Résultats: Un total de 14 689 pharmaciens ont été inclus dans l'étude : 7403 (50,4 %) diplômés canadiens et 7286 (49,6 %) DIP. Ces pharmaciens travaillaient dans 5028 pharmacies accréditées au total (243 pharmacies en milieu hospitalier [4,8 %] et 4785 pharmacies communautaires [95,2 %]). Parmi les diplômés canadiens, 2458 (33,2 %) ont signalé au moins un site de pratique en pharmacie hospitalière, tandis que la proportion était beaucoup plus faible parmi les DIP (427, 5,9 %). Les diplômés canadiens représentaient 85,2 % (2458/2885) de tous les pharmaciens ayant signalé une pratique de la pharmacie en milieu hospitalier. Le rapport de cotes (RC) brut estimé pour la pratique en pharmacie en milieu hospitalier était de 7,98 (IC à 95 % 7,16­8,91), et le RC ajusté était de 7,12 (IC à 95 % 6,39­7,98). Conclusions: Les DIP peuvent être confrontés à des obstacles qui entravent leur capacité à exercer dans un environnement hospitalier. Offrir des occasions, comme des formations cliniques structurées et des stages expérientiels, pourrait faciliter leur intégration dans des milieux institutionnels.

Real-World Use of Electronic Patient-Reported Outcome (ePRO) Tools Integrated in the Electronic Medical Record During Radiation Therapy for Head and Neck Cancer: Feasibility Study.

Purpose Use of electronic patient-reported outcome (ePRO) tools in routine oncology practice can be challenging despite evidence showing they can improve survival, improve patient and practitioner satisfaction, and reduce medical resource utilization. Head and neck cancer (HNC) patients receiving radiation therapy (RT) may be a group that would particularly benefit from interventions focused on early symptom management. Methods Patients undergoing definitive RT for HNC were enrolled in a feasibility study and received ePRO surveys integrated within the electronic medical record (EMR) on a weekly basis during RT. After completion of each ePRO survey, a radiation oncology registered nurse documented the findings and subsequent interventions within the EMR. Results Thirty-four patients with HNC who received curative RT at a single center were enrolled. The total number of surveys completed was 194 with a median of 7 surveys per patient (range 1-8). There was a total of 887 individual abnormal findings reported on the ePROs, and the authors found that all 887 had a corresponding documented intervention. Post-treatment practitioner questionnaires highlighted that ePROs were felt to be helpful for the care team in providing care to HNC patients. Conclusion For patients with HNC receiving RT, ePROs can be effectively utilized to address patient symptoms within an integrated health care system. Creating an infrastructure for the use of ePROs integrated within the EMR in routine care requires an approach that accounts for local workflows and buy-in from patients and the entire care team.

Regulatory T cells targeting a pathogenic MHC class II: Insulin peptide epitope postpone spontaneous autoimmune diabetes.

Introduction: In spontaneous type 1 diabetes (T1D) non-obese diabetic (NOD) mice, the insulin B chain peptide 9-23 (B:9-23) can bind to the MHC class II molecule (IAg7) in register 3 (R3), creating a bimolecular IAg7/InsulinB:9-23 register 3 conformational epitope (InsB:R3). Previously, we showed that the InsB:R3-specific chimeric antigen receptor (CAR), constructed using an InsB:R3-monoclonal antibody, could guide CAR-expressing CD8 T cells to migrate to the islets and pancreatic lymph nodes. Regulatory T cells (Tregs) specific for an islet antigen can broadly suppress various pathogenic immune cells in the islets and effectively halt the progression of islet destruction. Therefore, we hypothesized that InsB:R3 specific Tregs would suppress autoimmune reactivity in islets and efficiently protect against T1D. Methods: To test our hypothesis, we produced InsB:R3-Tregs and tested their disease-protective effects in spontaneous T1D NOD.CD28-/- mice. Results: InsB:R3-CAR expressing Tregs secrete IL-10 dominated cytokines upon engagement with InsB:R3 antigens. A single infusion of InsB:R3 Tregs delayed the onset of T1D in 95% of treated mice, with 35% maintaining euglycemia for two healthy lifespans, readily home to the relevant target whereas control Tregs did not. Our data demonstrate that Tregs specific for MHC class II: Insulin peptide epitope (MHCII/Insulin) protect mice against T1D more efficiently than polyclonal Tregs lacking islet antigen specificity, suggesting that the MHC II/insulin-specific Treg approach is a promising immune therapy for safely preventing T1D.

Antithrombotics and Gastrointestinal Prophylaxis: A Systematic Review.

Antithrombotic medications include both antiplatelet and anticoagulants and are used for a wide variety of cardiovascular conditions. A common complication of antithrombotic use is gastrointestinal bleeding. As a result, gastrointestinal prophylaxis is a common consideration for patients on a single or combination antithrombotic regimen. Prophylaxis is typically achieved through use of either proton pump inhibitors or histamine 2 receptor antagonists. Current recommendations for use of gastrointestinal prophylaxis with concomitant use of antithrombotic medications are scarce. In this systematic review, we explore the current evidence and recommendations regarding gastrointestinal prophylaxis for patients on antiplatelet or anticoagulant therapy as well as combination regimens.

Recommendations to address key recruitment challenges of Alzheimer's disease clinical trials.

Clinical trials for Alzheimer's disease (AD) are slower to enroll study participants, take longer to complete, and are more expensive than trials in most other therapeutic areas. The recruitment and retention of a large number of qualified, diverse volunteers to participate in clinical research studies remain among the key barriers to the successful completion of AD clinical trials. An advisory panel of experts from academia, patient-advocacy organizations, philanthropy, non-profit, government, and industry convened in 2020 to assess the critical challenges facing recruitment in Alzheimer's clinical trials and develop a set of recommendations to overcome them. This paper briefly reviews existing challenges in AD clinical research and discusses the feasibility and implications of the panel's recommendations for actionable and inclusive solutions to accelerate the development of novel therapies for AD.

Identifying distracted-driving events from on-road observations using a moving vehicle: A case study in New Jersey.

Distracted driving is a major traffic safety concern in the USA. To observe and detect distracted-driving events, various methods (e.g., surveys, videos, and simulations) involving the collection of cross-sectional data from individual subjects have been used in the transportation field. In this study, we employed an unconventional approach of on-road observations using a moving vehicle to collect data on distracted-driving events for multiple subjects in New Jersey. A data-collection crew member continuously navigated selected corridors to record driver-distraction events. A GPS (Global Positioning System) tracker was used to timestamp and record the location of each incident. Two non-parametric tests (Mann-Whitney U test and Kruskal-Wallis test) were performed to identify the significance of the variations in distracted-driving behaviors due to changes in temporal variables (e.g., day of the week, season), the type of roadway, and the geometric properties of the roadway. The results indicated that cellphone use was the leading type of distraction. Additionally, "handheld phone use (phone to ear)," "fidgeting/grooming," "drinking/eating/smoking," and "talking to passengers" events were significantly affected by the time of day and the geometric properties of the roadway. The results of this study are expected to assist state and local agencies in promoting awareness of distracted driving with the aim of reducing the frequency and severity of distracted driving-related crashes.

Serotonin Syndrome Induced Tako-Tsubo Syndrome.

Tako-tsubo syndrome is characterized by temporary systolic dysfunction of the left ventricle in the absence of coronary artery disease. Serotonin syndrome is a life-threatening condition associated with increased serotonergic activity in the central nervous system (CNS). We report a case of Tako-tsubo syndrome following seizures secondary to serotonin syndrome.

Myelodysplastic syndrome in a case of new-onset pancytopenia.

Myelodysplastic syndrome (MDS) is an infrequent cause of pancytopenia, which is a decrease in all three peripheral blood cell lines. We report the case of new-onset pancytopenia following administration of a COVID-19 vaccine and recurrent Zosyn use who was later found to have myelodysplastic syndrome.

The effects of repetition on belief in naturalistic settings.

In our modern well-connected world, false information spreads quickly and is often repeated multiple times. From laboratory studies, we know that this repetition can be harmful as repetition increases belief. However, it is unclear how repetition affects belief in real-world settings. Here we examine a larger number of repetitions (16), more realistic timing of the repetitions (across 2 weeks), and more naturalistic exposures (text messages). Four hundred thirty five U.S. participants recruited from mTurk were texted true and false trivia statements across 15 days before rating the accuracy of each statement. Statements were seen either one, two, four, eight, or 16 times. We find clear evidence that repetition increases belief. Initial repetitions produced the largest increase in perceived truth, but belief continued to increase with additional repetitions. We introduce a simple computational model suggesting that current accounts are insufficient to explain this observed pattern and that additional theoretical assumptions (e.g., that initial repetitions are more strongly encoded) are required. Practically, the results imply that repeated exposure to false information during daily life can increase belief in that misinformation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Abiotrophia defectiva Infective Endocarditis: A Rare and Dangerous Cause of Endocarditis.

Infective endocarditis is an uncommon heart infection, typically involving heart valves. Abiotrophia defectiva is a rare cause of endocarditis, typically found within the GI tract, and is usually difficult to isolate and requires specialized media. We report a case of Abiotrophia defectiva endocarditis following a root canal.

Pre-medication protocols for the prevention of paclitaxel-induced infusion related reactions: a systematic review and meta-analysis.

BACKGROUND: Prophylaxis against infusion-related reactions (IRR) from paclitaxel with steroids and antihistamines is a standard of care due to high rates of IRR. This systematic review and meta-analysis aimed to comprehensively summarize the evidence behind various prophylaxis strategies. METHODS: EMBASE, MEDLINE, PubMed, and the Cochrane Register of Controlled Trials were searched (1946 to May 14, 2021). The primary outcomes were Grade 3/4 IRR and any-grade IRR. Secondary outcomes included treatment delay or discontinuation and adverse events secondary to pre-medications. RESULTS: Of the 1285 unique citations, 26 studies were selected: 11 studies for quantitative analysis and 15 studies for qualitative analysis. Studies included randomized controlled trials and observational studies (n = 25-281). There was a non-significant benefit in favour of oral steroids starting 12 h prior to paclitaxel administration versus intravenous steroids immediately prior to paclitaxel administration for grade 3/4 IRRs, with a risk difference (RD) of 2% [95%CI 0 to 5%], any-grade IRR with a RD of 4% [95%CI: -1% to 9%] and treatment discontinuation with a RD of 1% [95%CI -1% to 2%]. For de-escalation strategies, a point-estimate for any-grade IRR was 0.44% [95% CI, 0 to 0.02, p = 0.98] and for grade 3/4 IRR was 3.1% (95% CI, 0.02 to 0.07, p = 0.11). CONCLUSION: Although studies have high risk of bias and risk, differences between steroid routes of administration were small, there was a non-significant trend in favour of oral steroids. De-escalation strategies after two previous successful paclitaxel infusions have an overall low incidence rate of severe IRR and warrant further prospective clinical trials. Insufficient evidence remains to recommend for or against other interventions for the prevention of paclitaxel IRR.

Neoplastic nerve lesions.

Though metastasis and malignant infiltration of the peripheral nervous system is relatively rare, physicians should have a familiarity with their presentations to allow for prompt diagnosis and initiation of treatment. This article will review the clinical presentations, diagnostic evaluation, and treatment of neoplastic involvement of the cranial nerves, nerve roots, peripheral nerves, and muscle. Due to the proximity of the neural structure traversing the skull base, metastasis to this region results in distinctive syndromes, most often associated with breast, lung, and prostate cancer. Metastatic involvement of the nerve roots is uncommon, apart from leptomeningeal carcinomatosis and bony metastasis with resultant nerve root damage, and is characterized by significant pain, weakness, and numbness of an extremity. Neoplasms may metastasize or infiltrate the brachial and lumbosacral plexuses resulting in progressive and painful sensory and motor deficits. Differentiating neoplastic involvement from radiation-induced injury is of paramount importance as it dictates treatment and prognosis. Neurolymphomatosis, due to malignant lymphocytic infiltration of the cranial nerves, nerve roots, plexuses, and peripheral nerves, deserves special attention given its myriad presentations, often mimicking acquired demyelinating neuropathies.

Prevalence and clinical outcomes of pleural effusion in COVID-19 patients: A systematic review and meta-analysis.

Observational studies indicate that pleural effusion has an association with risk and the clinical prognosis of COVID-19 disease; however, the available literature on this area is inconsistent. The objective of this systematic review and meta-analysis is to evaluate the correlation between COVID-19 disease and pleural effusion. A rigorous literature search was conducted using multiple databases. All eligible observational studies were included from around the globe. The pooled prevalence and associated 95% confidence interval (CI) were calculated using the random effect model. Mantel-Haenszel odds ratios were produced to report overall effect size using random effect models for severity and mortality outcomes. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 23 studies including 6234 COVID-19 patients was obtained. The overall prevalence of pleural effusion in COVID-19 patients was 9.55% (95% CI, I2 = 92%). Our findings also indicated that the presence of pleural effusions associated with increased risk of severity of disease(OR = 5.08, 95% CI 3.14-8.22, I2 = 77.4%) and mortality due to illness(OR = 4.53, 95% CI 2.16-9.49, I2 = 66%) compared with patients without pleural effusion. Sensitivity analyses illustrated a similar effect size while decreasing the heterogeneity. No significant publication bias was evident in the meta-analysis. The presence of pleural effusion can assist as a prognostic factor to evaluate the risk of worse outcomes in COVID-19 patients hence, it is recommended that hospitalized COVID-19 patients with pleural effusion should be managed on an early basis.

Seeding metastases: The role and clinical utility of circulating tumour cells.

Peripheral human blood is a readily-accessible source of patient material in which circulating tumour cells (CTCs) can be found. Their isolation and characterization holds the potential to provide prognostic value for various solid cancers. Enumeration of CTCs from blood is becoming a common practice in informing prognosis and may guide therapy decisions. It is further recognized that enumeration alone does not capture perspective on the heterogeneity of tumours and varying functional abilities of the CTCs to interact with the secondary microenvironment. Characterizing the isolated CTCs further, in particular assessing their functional abilities, can track molecular changes in the disease progress. As a step towards identifying a suite of functional features of CTCs that could aid in clinical decisions, developing a CTC isolation technique based on extracellular matrix (ECM) interactions may provide a more solid foundation for isolating the cells of interest. Techniques based on size, charge, density, and single biomarkers are not sufficient as they underutilize other characteristics of cancer cells. The ability of cancer cells to interact with ECM proteins presents an opportunity to utilize their full character in capturing, and also allows assessment of the features that reveal how cells might behave at secondary sites during metastasis. This article will review some common techniques and recent advances in CTC capture technologies. It will further explore the heterogeneity of the CTC population, challenges they experience in their metastatic journey, and the advantages of utilizing an ECM-based platform for CTC capture. Lastly, we will discuss how tailored ECM approaches may present an optimal platform to capture an influential heterogeneous population of CTCs.