bluuebunny/crossref_metadata_2025 huggingface dataset:
Septic Pulmonary Embolism in Pediatric Population: A Case Series With Literature Review
Authors: Hanna Issa , Gonzalez Vincent B. , Koul Pulin B.
Published: February 2025

Background:

Septic pulmonary embolism (SPE), resulting from infections such as osteomyelitis and endocarditis, is rare and lacks specific diagnostic guidelines. This report reviews the clinical manifestations, radiographic abnormalities and antibiotic therapy in children with SPE.

Methods:

Patients aged 1 to 18 years with confirmed SPE were identified from a database using the International Classification of Diseases-9/10 codes from 2000 to 2020. After excluding duplicates and those with neoplastic disease, 8 patients were included out of 16 encounters.

Results:

Patients predominantly presented with shortness of breath, fever and chest pain. Half had identifiable extrapulmonary infection sources. Leukocytosis was present in 50% and leukopenia in 12.5%. Anemia was noted in 87.5% of patients, possibly linked to patients’ acute illness. Contrasted chest computed tomography showed bilateral emboli in most patients. Echocardiograms were normal. Methicillin-resistant Staphylococcus aureus was identified in 62.5% of cases and oxacillin-sensitive staphylococcus aureus in 37.5%. While osteomyelitis was the most common infection source, our series uniquely included cavernous sinus thrombosis in children and reported for the first time. Most patients were empirically treated with vancomycin.

Conclusion:

This case series highlights cavernous sinus thrombosis as a new clinical entity associated with pediatric SPE. It emphasizes the significance of prompt, targeted antibiotic therapy for improved outcomes in children with SPE.
Gunshot injury to the left side of the neck with the lodged bullet in the carotid sheath: A case report
Authors: Jahanshahi Fatemeh , Saberi Ali
Published: February 2025

Rationale:

Penetrating neck trauma involving the carotid artery is rare but highly lethal, requiring prompt and accurate diagnosis followed by immediate surgical intervention.

Patient concerns:

A 20-year-old male presented with a high-velocity gunshot wound to the left side of the neck. Despite the severity of the injury, the patient was asymptomatic and hemodynamically stable.

Diagnose:

Initial evaluation, including ultrasound imaging, revealed a bullet lodged within the left common carotid artery.

Interventions:

Due to the high risk of vascular complications, the patient underwent emergency surgery. The damaged artery segment was resected, and a primary end-to-end anastomosis was performed.

Outcomes:

The patient recovered well and was discharged without neurological deficits.

Lessons:

Early diagnosis and intervention are crucial in carotid artery injuries. This case demonstrates the limitations of computed tomography angiography in the presence of metallic artifacts and highlights the effectiveness of ultrasound for accurate diagnosis. Although penetrating neck injury management protocols typically recommend conservative management for asymptomatic Zone 2 injuries, surgical intervention is necessary due to the high-risk features of similar cases when the foreign object remains inside, and there is a risk of movement and severe damage. Adaptation of protocols based on individual injury characteristics can enhance patient outcomes. Although this is a rare case, similar cases have been reported, and it highlights the need to update the penetrating neck injury management protocols for the management of similar cases.
Exploring the mechanism of action of Lobetyolin in the treatment of allergic rhinitis based on network pharmacology and molecular docking
Authors: Hou Li , Yang Jing , Li Yanrong , Kang Jing , Ma Zheng , Luo Xiaoya , Yang Xiaoling , Shao Hui
Published: February 2025

Lobetyolin (LBT) is an important active ingredient in the traditional medicinal plant Codonopsis pilosula (Franch.) Nannf. However, the pharmacological targets and mechanisms of action of LBT against allergic rhinitis (AR) are not known. The aim of this study was to evaluate the possible functional role and potential mechanism of LBT as an anti-AR treatment through a combination of network pharmacology and molecular docking. The disease database and target screening database were used to find potential targets for screening LBT for the treatment of AR. Further network visualization analysis, gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for potential targets. Finally, we performed some molecular docking with LBT and core targets to verify their relevant effects. The results revealed that a total of 64 target genes were obtained for LBT for AR. The top 10 targets with the highest enrichment scores were tumor necrosis factor, epidermal growth factor receptor, matrix metalloproteinase 9, recombinant toll-like receptor 4, erb-b2 receptor tyrosine kinase 2, JUN protooncogene, C-X-C motif chemokine receptor 4, HSP90AA1, kinase insert domain receptor, and matrix metalloproteinase 2. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that multiple signaling pathways are involved in LBT for AR. Molecular docking results showed that LBT binds strongly to the target proteins matrix metalloproteinase 2, matrix metalloproteinase 9, tumor necrosis factor, JUN protooncogene, and epidermal growth factor receptor through intermolecular forces. This study reveals for the first time the pharmacological targets and related pathways of LBT for the treatment of AR, indicating that LBT can intervene in the intrinsic molecular mechanism of AR through multiple targets and pathways.
A comparative evaluation of alectinib for ALK-positive non-small-cell lung cancer: A systematic review
Authors: Kharat Monica , Nookala Harshitha , John Jabez David , Patel Tirath , Kalyandrug Pragnesh , Emmanuel Sonya , Noor Anaya , Halani Dhruv Jignesh Kumar , Goyal Abhishek , Anand Nikhilesh , Gadad Bharathi , Millis Richard M.
Published: February 2025

Background:

Lung cancer, a significant global health challenge, notably the non-small-cell lung cancer (NSCLC) subtype, is a topic of utmost importance. The continuous advancements in NSCLC treatment, especially in the context of anaplastic lymphoma kinase (ALK)-positive NSCLC, are of great interest. A thorough review of alectinib’s comparative efficacy and safety with other treatment modalities is a crucial step, and the role of clinicians and surgeons is integral in optimizing patient care. This review can also inform neoadjuvant therapies and enhance surgical education, facilitating more informed decision-making processes between surgeons and patients.

Methods:

This comprehensive systematic review results from rigorous screening. Following a rigorous screening process of the PubMed, PubMed Central, and Medline databases by quality assessment and application of inclusion/exclusion criteria filters, 9 relevant articles were identified that directly addressed the research question and provided a holistic understanding of it. The analysis included a total of 1403 patients from 9 different studies. Alectinib was given to 836 patients, while 567 patients received other chemotherapeutic drugs. The primary objective of this study was to evaluate and compare the efficacy of alectinib with other treatment modalities.

Results:

The analysis revealed that alectinib is promising for ALK-positive NSCLC cases, with significantly better efficacy and a positive impact on limiting central nervous system metastases. Alectinib’s favorable safety profile, with medically manageable adverse events, provides reassurance about its safety compared with other treatment modalities.

Conclusions:

Alectinib has emerged as a viable, significantly superior treatment option for patients with ALK-positive NSCLC. The superior efficacy and manageable safety profile are significant; it remains a novel therapy with much potential, such as neoadjuvant therapy, which will make significant strides in patient care of ALK-positive NSCLC. Therefore, it is crucial for healthcare professionals, including surgeons, to be well-versed in alectinib and its potential. This knowledge will empower them and instill confidence in their ability to provide the best care for their patients.
Diabetes mellitus, metformin’s target gene AMPK, and inflammatory bowel disease: A Mendelian randomization study
Authors: Wu Wei , Tong Huomu , Li Yunsheng , Cui Jia
Published: February 2025

The causal relationship between inflammatory bowel disease (IBD) and diabetes mellitus remains unclear. The aim of this study was to delve into this association and investigate the correlation between AMP-activated protein kinase (AMPK), a target gene of metformin, and the risk of developing IBD. Researchers conducted a bidirectional two-sample Mendelian randomization analysis to examine causal relationships between IBD, including ulcerative colitis and Crohn disease (CD), and diabetes mellitus, encompassing both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Additionally, this study utilized AMPK-related variants associated with HbA1c (%) as instrumental variables for the metformin target gene AMPK to further investigate their association with the risk of IBD. The inverse variance weighted method was used as the primary analytical approach. Mendelian randomization analysis revealed a suggestive association between IBD and T1DM (P = .024). CD was associated with an increased risk of T1DM (P = .011). In the reverse analysis, T1DM also increased the risk of IBD (P = .043). No causal relationship was found between IBD and T2DM in either the forward or reverse analyses. In addition, this study did not find any significant effect of AMPK on IBD. In conclusion, this study suggests a bidirectional association between IBD and T1DM, in which CD may increase the risk of T1DM. However, no causal relationship was found between IBD and T2DM. Furthermore, our findings revealed that the metformin’s target gene AMPK had no significant effect on the onset of IBD.
Gut-disc axis: A Mendelian randomization study on the relationship between gut microbiota and cervical spondylosis
Authors: Zhang Jiling , Wang Baodong , Du Peng , Song He , Yang Lihui , Zhou Yu
Published: February 2025

The gut-disc axis, which refers to the interaction between gut microbiota and bone health, has recently garnered widespread attention in the scientific community. However, it remains to be determined whether gut microbiota directly induces cervical spondylosis (CS). This study employed a bidirectional 2-sample Mendelian randomization (MR) analysis to explore the potential causal link between gut microbiota and CS. We initially used the inverse variance weighted method for preliminary estimation and supplemented it with other MR methods, including MR-Egger, weighted median, weighted mode, and simple mode. Furthermore, we utilized the Cochrane Q test, MR-PRESSO global test, and MR-Egger intercept test to assess possible pleiotropy and heterogeneity. Ultimately, we conducted a bidirectional MR study to investigate potential reverse associations between gut microbiota and CS. The preliminary MR analysis identified 27 gut microbiota significantly associated with CS, of which 12 may be contributing factors, while 15 may have protective effects. The reverse MR analysis further revealed a potential causal relationship between CS and 24 gut microbiota. In this study, no significant heterogeneity or pleiotropy was detected. Through MR analysis, we uncovered a significant causal relationship between gut microbiota and CS, providing new perspectives for the prevention and treatment of CS, especially in the modulation of the microbiota.
Epidemiologic evaluation of pediatric patients receiving high-flow nasal cannula therapy in the pediatric emergency department
Authors: Baykara Sayili Sena , Keskin Bedirhan , Uysalol Metin
Published: February 2025

High-flow nasal cannula (HFNC) therapy has emerged as an important method of respiratory support in the pediatric emergency department (ED), but its optimal use and factors affecting success require further investigation. The aim of this study was to evaluate the diagnosis and treatment response of patients receiving HFNC therapy in the pediatric ED and to investigate the factors affecting the success of HFNC therapy. This retrospective, cross-sectional study analyzed the data of 415 patients admitted to the Pediatric ED of the Istanbul Medical Faculty from 2021 to 2022 who received HFNC therapy. Treatment failure was defined as the required noninvasive ventilation (NIV) or intubation. Diagnoses were confirmed by examination findings, radiological imaging, laboratory tests and other hospital admissions. Respiratory disease was diagnosed in 88.2% of patients. The most common diagnoses were bronchiolitis (48%), pneumonia (23.6%), asthma (9.6%), reactive airway disease (5.8%), and heart failure (4.8%). Among the patients, 55.4% were admitted to the pediatric service, 28% were admitted to the intensive care unit, 8.7% were discharged, and 7.7% left the ED with a referral to an external center. HFNC therapy ended with symptom regression in 63.9% of patients, transition to NIV in 25.8%, and intubation in 4.3%. Although patients did not respond to HFNC therapy at 0 to 1 hour, a HFNC response was observed in almost half of the patients in the following periods. The presence of chronic disease and abnormal chest radiography findings were found to be independent risk factors for treatment failure, whereas the presence of allergic disease and the duration of HFNC therapy were found to be protective factors. HFNC therapy was effective in most pediatric patients with respiratory distress. Clinicians should consider extending HFNC therapy beyond the first hour in initial nonresponders, as significant improvement may occur in the following hours. Chronic disease and abnormal chest radiography findings were independent risk factors for failure of HFNC therapy. Conversely, allergic disease and longer HFNC duration were protective. Clinical and laboratory parameters should be considered when evaluating the efficacy of HFNC therapy. Therefore, patients should be evaluated individually, and treatment should be planned.
Effect of early readmission on subsequent hospital admissions within 1 year in patients with heart failure: A retrospective cohort study
Authors: Liang Mengyao , Yang Qingqing , Lu Yi , Wang Yanmei
Published: February 2025

This study aimed to identify the factors influencing multiple admissions within 1 year for patients with heart failure (HF) and to examine the impact of early readmission on subsequent admissions. A retrospective questionnaire survey was conducted on 498 patients with HF admitted to our hospital’s Cardiology department between January 1, 2020, and December 31, 2022. Multivariate regression analysis identified factors influencing multiple admissions, and propensity score matching (PSM) assessed the impact of readmissions within 30 days and 31 to 90 days post-discharge on unplanned admissions within a year. The incidence of multiple admissions was 22.09% (110/498), with first readmissions within 30 days post-discharge at 13.25% (66/498) and within 31 to 90 days at 15.86% (79/498). Influential factors for multiple unplanned hospital admissions included age, history of atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, New York Heart Association grade ≥ III, hemoglobin (Hb) < 110g/L, taking 7 or more medications, and readmission within 31 to 90 days (P < .05). Post-PSM analysis showed that the first admission within 30 days (odds ratio [OR] = 6.400, 95% confidence interval [Cl] = 2.638–15.527, P = .001), and the first admission within 31 to 90 days significantly increased the risk of multiple admissions (OR = 5.694, 95% Cl = 2.615–12.402, P = .001). Patients with HF exhibit a high rate of numerous readmissions within 1 year. Clinical medical staff should focus more on patients with early readmissions, enhance self-management, and improve management of comorbidities and medications through a multidisciplinary team approach. Enhancing continuous nursing and improving access to medical services may reduce patient readmission rates.
Does Family History and Knowing a Friend With Breast Cancer Predict Cancer Knowledge and Screening Practices? An International Study of Asian Women
Authors: Lee Chun Fan , Kwok Cannas , Lee Mi-Joung
Published: February 2025

Background

Family history of breast cancer and social networks were found to have an influential effect on women’s cancer knowledge and screening practices. There is a scarcity of studies in this area among Asian populations.

Objective

This study aimed to explore the effect of family history and knowing a friend with breast cancer on Chinese and Korean women’s knowledge of breast cancer and screening practices.

Methods

A convenience sample of 742 women, comprising 493 and 249 Chinese and Korean women, respectively, was recruited. Data were collected by the Chinese and Korean version of the Breast Cancer Screening Beliefs Questionnaire. Multivariable linear regression was performed to answer the research question.

Results

Korean women with neither family history nor a friend history had significantly higher scores in all 3 subscales of the BCBSQ compared with their Chinese counterparts. In contrast, no significant differences were found between the 2 cohorts in women who have either family history or a friend history. Comparing within the Chinese cohort, women with a friend history obtained a significantly higher score in all 3 subscales of BCBSQ than those without a friend history. Similar significant association was found between having a friend history and screening practices in both cohorts.

Conclusion

Knowing a friend with breast cancer is an influential factor that impacts women’s cancer knowledge and screening practices.

Implications for Practice

The concept of peer influence should be incorporated into the design of breast cancer awareness and screening promotion programs for women from these cultural backgrounds.
Awareness, attitudes, and interest in doxyPEP as bacterial prophylaxis against sexually transmitted infections - New York City Sexual Health Clinics, June-August 2023
Authors: Leocadio Ciarra , Betancourt Gabriela , Tang Jennifer , Heth Zachary , Pathela Preeti
Published: February 2025

Background: Increased incidence of bacterial sexually transmitted infections including chlamydia, gonorrhea, and syphilis dictates the need for novel prevention strategies. One such strategy, doxycycline prescribed prophylactically, has proven to be effective at reducing transmission among men who have sex with men (MSM) and transgender women. We assessed awareness, attitudes, and interest in doxycycline pre-exposure/post-exposure prophylaxis (doxyPrEP/doxyPEP) among New York City (NYC) Sexual Health Clinic (SHC) patients, including MSM, other cisgender men, women, transgender persons, and patients identifying as gender non-conforming or non-binary.

Methods: A self-administered survey was completed by 280 patients from five NYC SHCs between June-August 2023 that collected information assessing their knowledge, concerns, and willingness to use doxyPrEP and doxyPEP. We used Poisson regression models to examine factors associated with willingness to use doxyPEP.

Results: Of the 280 patients, 73% (205) and 55% (153) reported they would take doxyPEP and doxyPrEP, respectively, if offered by their provider. Willingness to use doxyPEP was observed across gender groups and significantly associated with history or current use of HIV pre-exposure prophylaxis (adjusted risk ratio (aRR) 1.17, 95% CI: 1.07-1.27). Compared to non-Hispanic white participants, Hispanic (aRR 1.27, 95% CI: 1.07-1.52) and Non-Hispanic Other (Alaskan Native, American Indian, Native Hawaiian, Pacific Islander, multiracial) group (aRR 1.28, 95% CI: 1.06-1.56) participants were more likely to report willingness to use doxyPEP. Possible antibiotic resistance was of highest concern.

Conclusions: If offered by a provider, doxyPEP would likely be accepted by patients of all gender groups. Additional research on acceptability in other settings would help guide widespread implementation.
Estimation of Vitreous Chamber Volume Using Axial Length Measurements
Authors: Huang Yihong , Zhang Yan , Chen Wanzhu , Xiao Yanling , Huang Guangqian , Wu Yuyu , Cai Chi , Guo Maosheng
Published: February 2025

Background:

Vitreous chamber volume (VCV) in humans can be accurately measured using magnetic resonance imaging (MRI) combined with ITK-SNAP analysis software. This study explores the relationship between VCV and axial length (AL).

Methods:

This study included 46 healthy individuals, encompassing a total of 92 eyes. Individuals with a history of eye conditions were excluded from the study. AL measurements were obtained using the Lenstar 900 (Haag-Streit, Switzerland). VCV was assessed through MRI using the Ingenia 3.0T system (Philips Medical Systems, Netherlands), with VCV analysis performed using ITK-SNAP analysis software version 3.8.0. The correlation between AL and VCV was evaluated using Pearson linear correlation coefficient, and a logistic regression model was employed to predict VCV.

Results:

The sample consisted of 92 eyes from 46 individuals, including 28 women and 18 men. The average VCV was 6193±1135.9 mm3 for women and 6324.3±886.7 mm3 for men. The mean AL for women was 24.70±2.78 mm, while for men it was 24.66±1.70 mm. A significant correlation between AL and VCV was observed (P<0.001).

Conclusions:

VCV can be accurately estimated through AL measurements, offering a clinically relevant method for assessing VCV.
3D Deep Learning for Virtual Orbital Defect Reconstruction: A Precise and Automated Approach
Authors: Yu Fangfang , Liu Chang , Zhong Chenglan , Zeng Wei , Chen Jinlong , Liu Wei , Guo Jixiang , Tang Wei
Published: February 2025

Accurate virtual orbital reconstruction is crucial for preoperative planning. Traditional methods, such as the mirroring technique, are unsuitable for orbital defects involving both sides of the midline and are time-consuming and labor-intensive. This study introduces a modified 3D U-Net+++ architecture for orbital defects reconstruction, aiming to enhance precision and automation. The model was trained and tested with 300 synthetic defects from cranial spiral CT scans. The method was validated in 15 clinical cases of orbital fractures and evaluated using quantitative metrics, visual assessments, and a 5-point Likert scale, by 3 surgeons. For synthetic defect reconstruction, the network achieved a 95% Hausdorff distance (HD95) of<2.0 mm, an average symmetric surface distance (ASSD) of ∼0.02 mm, a surface Dice similarity coefficient (Surface DSC)>0.94, a peak signal-to-noise ratio (PSNR)>35 dB, and a structural similarity index (SSIM)>0.98, outperforming the compared state-of-the-art networks. For clinical cases, the average 5-point Likert scale scores for structural integrity, edge consistency, and overall morphology were>4, with no significant difference between unilateral and bilateral/trans-midline defects. For clinical unilateral defect reconstruction, the HD95 was ∼2.5 mm, ASSD<0.02 mm, Surface DSC>0.91, PSNR>30 dB, and SSIM>0.99. The automatic reconstruction process took ∼10 seconds per case. In conclusion, this method offers a precise and highly automated solution for orbital defect reconstruction, particularly for bilateral and trans-midline defects. We anticipate that this method will significantly assist future clinical practice.
Achieving Reliable Mastery of Emergency Airway Management Skills Through 4-Component Instructional Design
Authors: Gilic Fil , McGraw Robert , Newbigging Joseph , Blackmore Elizabeth , Stacey Matthew , Mercer Colin , Neufeld Troy , Johannessen Erika , Lam Wilson , Hall Ryan , Braund Heather
Published: February 2025

Introduction

We used cognitive load theory to design the Queen's University Airway Mastery (QUMAC) pilot course to work toward reliable mastery of Emergency Airways Management elements in all participants.

Methods

We describe the process of designing QUMAC using 4-Component Instructional Design to harness the cognitive load theory as a learning tool. We evaluated the effectiveness of QUMAC using an outcome-based mixed-methods approach including Objective Structured Assessment of Technical Skills (OSATS) and 2 Objective Structured Clinical Examinations (OSCEs) at course completion using blinded expert video review. We also conducted semistructured interviews at course completion and after 6 months of independent practice. Interviews were analyzed thematically.

Results

Mean OSCE Global Performance Scores were 4.1 (±0.56) of 5 for both OSCE scores; and 4.0–4.4 (±0.48–0.89) on OSATS. At course completion, 4 themes were identified: Overall Experience with the Course, Facilitators of Performance, Recommendations, and Transfer to Practice. At 6 months of independent practice 5 themes emerged: Level of Confidence, Management of Cognitive Load, Persistence, Barriers to Application, and Recommendations

Conclusions

All participants demonstrated a high degree of competence when assessed by OSCEs and majority did so with the OSATS. All noticed an increase in confidence and reduced cognitive load while managing airways. These persisted over 6 months of independent practice where the participants were actively managing airways as staff physicians in new workplaces. High performance expectations, automation, schemas, spaced repetition, and homework were the elements most associated with better performance and more confidence. Decreased cognitive load freed up resources for higher order thinking, while the overall sense of competence reduced the anxiety of going to work as a new emergency department staff.
Venous thromboembolism events in trauma patients after hospital discharge
Authors: Dougherty Jacob M. , Gerhardinger Laura J. , Johnson Patrick L. , Regenbogen Scott E. , Scott John W. , Sangji Naveen F. , Jean Raymond A. , Hemmila Mark R. , Oliphant Bryant W.
Published: February 2025

BACKGROUND

Venous thromboembolism (VTE) is common after major injury. This elevated VTE risk likely continues beyond hospital discharge, but a lack of postdischarge surveillance limits our understanding of this complication and opportunities for improving outcomes. We aimed to characterize the incidence and risk factors of trauma patients who developed a VTE in the first year after discharge from their index hospital admission.

METHODS

We used data from adult inpatients (18 years or older) from 35 American College of Surgeons - Committee on Trauma–verified Level 1 and Level 2 trauma centers in a statewide trauma quality improvement program from 2018 to 2023. The incidence and timing of a postdischarge VTE were identified from linked longitudinal insurance claims data, and multivariable logistic regression was performed to identify predictors of a postdischarge event.

RESULTS

Of 34,421 trauma registry and claims matched patients identified, 1,487 (4.3%) developed a VTE within the first year after discharge from the trauma center, compared with 280 VTE events (0.8%) diagnosed during the index admission. The incidence of VTE remained elevated well after discharge, with 40% occurring in the first 30 days and 73% within the first 3 months. Multiple patient, injury, and treatment factors were associated with postdischarge VTE risk, including having an operation, a significant spine injury, Black race, and receiving a blood transfusion.

CONCLUSION

The risk of VTE extends well beyond the index hospitalization for trauma patients, as the majority of events occur after discharge. Understanding and improving VTE outcomes in trauma patients will require a longitudinal patient record that captures these complications. Postdischarge VTEs are an underrecognized trauma-related morbidity but are also very treatable through a better understanding of the risk factors and the optimal prophylactic strategy.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
Predictive value of platelet function assays in traumatic brain injury patients on antiplatelet therapy
Authors: Alsaadi Nijmeh , Younes Reem , Killinger Jack R. , Hoteit Lara , Puccio Ava M. , McIntyre Peyton , Raymond Olivia , Filicky Amanda , Hahner Thomas , Agnone Allison G. , Vincent Laura E. , Srinivasan Amudan , Zarisfi Mohammadreza , Dishong Devin M. , Abdullah Abiha , Arivudainambi Aishwarrya , Kar Ronit , Mihalko Emily P. , Loughran Patricia , Wisniewski Stephen R. , Luther James F. , Spinella Philip C. , Okonkwo David , Guyette Francis X. , Sperry Jason L. , Shea Susan M. , Neal Matthew D.
Published: February 2025

INTRODUCTION

Traumatic brain injury (TBI) patients on antiplatelet therapy face higher mortality because of impaired platelet function, which may be treated by platelet transfusion. The value of testing platelet function in this cohort remains controversial. We aimed to evaluate the relationship between platelet function assays and outcomes in TBI patients on antiplatelet therapy receiving platelet transfusions. We hypothesized that the magnitude of change in platelet assay performance following a transfusion would predict meaningful clinical outcomes.

METHODS

A cohort of patients, aged 18 to 89 years, with a history of preinjury antiplatelet therapy or who required platelet transfusion, and who were deemed at risk for neurosurgical intervention, was selected from a prospective randomized controlled trial of platelet transfusion for TBI. Pre- and posttransfusion blood samples were drawn. Platelet hemostatic function assays (PHFAs) included thromboelastography with platelet mapping (TEG-PM) and VerifyNow. Logistic regression models assessed the association of temporal assay results with 30-day all-cause mortality, need for craniotomy, and initial and follow-up Rotterdam scores.

RESULTS

Data from 94 TBI patients (43% female) with a median age of 76 years were analyzed. The 30-day mortality rate was 14%. VerifyNow aspirin assay was able to capture increases in platelet function following a platelet transfusion in patients on aspirin (significant positive Δ = 65 aspirin response units, p < 0.001). Thromboelastography with platelet mapping parameters detected improved platelet function following transfusion, although the absolute value of changes was minimal. Thromboelastography with platelet mapping parameters predicted important clinical outcomes on logistic regression, although no significant associations with clinical outcomes were identified by the change in PHFA after transfusion or after adjusting for multiple comparisons.

CONCLUSION

Higher absolute pre- and posttransfusion values of TEG-PM were associated with decreased mortality, decreased need for neurosurgical intervention, and decreased risk of progression of hemorrhage in TBI patients taking antiplatelet agents, although neither the change in TEG-PM after transfusion nor any other PHFA value predicted outcomes.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Who is being heard? Implementing change with people from diverse and marginalized groups in aged care: a scoping review
Authors: Marshall Amy , Windle Alice , Harvey Gill , Davy Carol
Published: February 2025

Introduction:

Many older people belong to diverse and marginalized groups, with care needs and preferences outside of normative aged care services. Increasing the representation and contributions of these older people is central to an equity-sensitive implementation approach where adaptation to the context is critical.

Objective:

This review assessed the extent and nature of the literature on implementing change in aged care contexts serving older people who belong to diverse and marginalized groups.

Methods:

This scoping review searched for literature examining the implementation of change in any aged care context where older people from diverse and marginalized groups access care. The search was conducted in the PubMed, CINAHL, Scopus, and PsycINFO databases, and limited to papers published from 2013 onward. Of the 2,021 papers identified, 35 were included.

Results:

The majority (70%) of studies were in a residential aged care context, and only 25% used an implementation framework. Less than half (40%) engaged with diverse and marginalized older people or their representatives to understand their needs and preferences. The majority engaged instead with staff or other stakeholders, and most engagement (64%) was limited to lower-level consultation such as seeking feedback rather than involving, collaborating, or empowering stakeholders to ensure their perspectives improved the implementation process.

Conclusions:

There is little in the literature about ensuring changes in aged care identify and meet the needs and priorities of diverse and marginalized older people. This suggests a pressing need for implementation science to pay greater attention to equity and inclusion in the aged care context.

Spanish abstract:

http://links.lww.com/IJEBH/A314
We are the champions, my friend! Key considerations in selecting and supporting champions to promote implementation in aged care
Authors: Windle Alice , Marshall Amy , Harvey Gillian , Davy Carol
Published: February 2025

Introduction:

Champions are a well-recognized strategy for supporting the implementation of innovations in care settings, yet there is limited clear guidance to support their use in the particular context of aged care.

Aim:

This study aimed to identify key lessons for optimizing the use of champions as an implementation strategy in aged care settings.

Methods:

We conducted a secondary analysis of literature included in a recent scoping review on implementing innovations in aged care.

Results:

The individuals who acted as champions came from a variety of roles and disciplines. The functions performed by champions largely involved influencing others, as well as other activities such as facilitating, educating, enabling, and reinforcing implementation. Key characteristics of champions included being enthusiastic and well-regarded by others, as well as having empathy and appropriate skills and knowledge. Champions were reportedly challenged by resourcing issues such as high workload, staff turnover, and competing priorities. The support of leaders and peers, a clearly identified role, adequate training, and appropriate selection were identified as key to optimizing champions’ effectiveness.

Conclusions:

For champions to be an effective implementation strategy, the champions need to be carefully selected, appropriately trained, and well supported. These findings can inform approaches to optimize the use of champions for implementing innovations in aged care.

Spanish abstract:

http://links.lww.com/IJEBH/A318
A prognostic model for Senescence-related LncRNA in a novel colon adenocarcinoma based on WGCNA and LASSO regression
Authors: Huang Yichu , Min Guangtao , Wang Hongpeng , Jiang Lei
Published: February 2025

Objective

This study aims to develop a prognostic model based on senescence-related long non-coding RNAs (lncRNAs) to predict the prognosis of patients with colon cancer and enhance their survival rates.

Method

Differential expression analysis and Pearson correlation were employed to identify senescence-related lncRNAs in colon cancer. A risk prognosis model was constructed using univariate Cox regression analysis and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The reliability of this model was validated through survival analysis, receiver operating characteristic (ROC) curves, bar charts, and calibration curves. Additionally, the relationship between the prognostic model, immune microenvironment, and drug sensitivity was explored.

Results

A risk prognosis model comprising eight senescence-related lncRNAs (LINC02257, AL138921.1, ATP2B1-AS1, AC005332.7, AC007728.3, AC018755.4, AL390719.3, THCAT158) was successfully established, demonstrating strong performance in predicting the overall survival rates of colon cancer patients. A significant correlation was observed between the senescence-related lncRNA progn model and the tumor microenvironment, immune infiltrating cells, and drug sensitivity.

Conclusion

The senescence-related lncRNA prognostic model developed in this study can accurately forecast the prognosis of colon cancer patients, offering new insights for personalized treatment approaches in colon cancer.
Transient Acute Neuronal Activation Response Caused by High Concentrations of Oligonucleotides in the Cerebral Spinal Fluid
Authors: Hernandez Mariana Bravo , Mazur Curt , Chen Hao , Fradkin Linda , Searcy Justin , Burel Sebastien , Kelly Mackenzie , Bruening Dona , O’Rourke Jacqueline G. , Cai Yuhang , Nguyen Jonathon , Berman-Booty Lisa , Cummins Lendell , Gaus Hans , Powers Berit , Zhao Hien , Jafar-Nejad Paymaan , Henry Scott , Swayze Eric , Kordasiewicz Holly B.
Published: February 2025

Oligonucleotide (ON) therapeutics are promising as a disease-modifying therapy for central nervous system disorders. Intrathecal ON administration into the cerebral spinal fluid is a safe and effective delivery mode to the CNS. However, preclinical studies have shown acute toxicities following high-dose central ON delivery. Here we characterize a transient neurobehavioral change peaking 15 minutes after ON dosing and resolving after 120 minutes. Symptoms include shaking, muscle twitching, cramping, hyperactivity, stereotypic movements, hyperreactivity, vocalizations, tremors, convulsions, and seizures. These are collectively referred here as the acute neuronal activation response. Acute neuronal activation is observed in rats, mice, and non-human primates and is quantifiable using a simple scoring system. It is distinct from acute sedation seen with some phosphorothioate-modified antisense oligonucleotides, characterized by loss of spinal reflexes, ataxia, and sedation. The acute neuronal activation response is largely sequence-independent and is driven by ON chelation of divalent cations, particularly influenced by the divalent cations-to-ON ratio in the dosing solution. Acute neuronal activation can be safely mitigated by adjusting this ratio through magnesium supplementation in the ON formulation. We provide a comprehensive framework for quantifying and mitigating the acute neuronal activation response caused by high concentrations of centrally delivered ON therapeutics in preclinical species.

GRAPHICAL ABSTRACT
Top-down control of the descending pain modulatory system drives placebo analgesia
Authors: Livrizzi Giulia , Liao Jingzhu , Johnson Desiree A. , Lubejko Susan T. , Chang-Weinberg Janie , Dong Chunyang , Tian Lin , Banghart Matthew R.
Published: February 2025

In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify the underlying neural circuits, we reverse-translated a conditioned placebo protocol from humans to mice. Surprisingly, the placebo effect suppresses both nociception and unconditioned emotional-motivational pain-related behavior. Descending pain modulatory neurons in the periaqueductal gray (PAG) are critical for both morphine and placebo antinociception. The placebo effect depends on input to the PAG from the medial prefrontal and anterior cingulate cortices, but not anterior insular cortex. Conditioning enhances noxious stimulus-evoked endogenous opioid release in the PAG to produce analgesia. Our results suggest that cortical control of the descending pain modulatory system (DPMS) is gated by rapid endogenous opioid signaling in the PAG during placebo trials. This study bridges clinical and preclinical research, establishing a central role for the DPMS in placebo analgesia.
The Association between Psoriasis and Risk of ST-Elevation Myocardial Infarction among African American Patients
Authors: Krdi Ghena , Sparling Kennedy , Movahed Mohammad Reza , Hashemzadeh Mehrtash , Hashemzadeh Mehrnoosh
Published: February 2025

Background/Objectives

Several studies have attempted to investigate the association between psoriasis and the incidence of cardiovascular disease (CVD) including ST-segment elevation myocardial infarction (STEMI), possibly making psoriasis a risk factor for the development of CVD. African American (AA) patients have a higher prevalence of cardiovascular disease risk factors, representing a racial health disparity. There are very limited studies on the association between psoriasis and STEMIs among this specific patient population. This study aims to explore if an association exists between a diagnosis of psoriasis and the incidence of STEMI among AA patients.

Methods

Patients with specific ICD-10 codes for psoriasis and STEMI were included from the National Inpatient Sample (NIS) data. The rates of STEMI in patients with an established diagnosis of psoriasis were calculated and compared between AA and non-AA patients. An additional multivariate analysis was performed to adjust for CVD risk factors including age, gender, hypertension, hyperlipidemia, smoking, and diabetes.

Results

The analysis revealed no significant association between a diagnosis of psoriasis and STEMI incidence among AA patients. However, there was a significant positive association between psoriasis and STEMIs with p-value <0.001 among the total population despite race. After adjusting for confounding variables, there remained no significant association between psoriasis and STEMI among AA patients, and there was a significant negative association between psoriasis and STEMI among non-AA patients.

Conclusion

These findings suggest that psoriasis is not directly associated with STEMI among AA and non-AA patients, especially when controlling for confounding risks. Given the low prevalence of psoriasis among AA patients and the large burden of CVD in this patient population, further research will need to be conducted possibly guiding early CVD risk assessment and psoriasis management in AA patients.
Transferrin receptor-binding blood-brain barrier shuttle enhances brain delivery and efficacy of a therapeutic anti-Aβ antibody
Authors: Vega Marta Ramos , Hansen Henrik H. , Jensen Camilla Stampe , Alexiou Evdoxia , Madsen Martin R , Wichern Franziska , Skytte Jacob Lercke , Salinas Casper Graversen , Sotty Florence , Jensen Allan , Vergo Sandra , Hecksher-Sørensen Jacob
Published: February 2025

Transferrin receptor-1 (TfR1) transcytosis-mediated delivery of therapeutic monoclonal antibodies across the blood-brain barrier (BBB) is a promising concept in drug development for CNS disorders. We sought to investigate brain delivery and efficacy of Aducanumab (Adu), an anti-Aβ antibody, when fused to a mouse TfR1-binding Fab fragment as BBB shuttle (TfR1-Adu). Automated 3D light sheet fluorescence imaging coupled with computational analysis was applied to evaluate drug IgG distribution and plaque counts throughout the intact brain of transgenic APP/PS1 mice. TfR1-Adu demonstrated enhanced brain delivery and more homogeneous distribution after both acute and chronic dosing in transgenic APP/PS1 mice compared with unmodified Adu. Also, importantly, only unmodified Adu showed perivascular labelling. While high-dose Adu promoted Aβ plaque depletion in multiple brain regions, similar plaque-clearing efficacy was achieved with a five-fold lower dose of TfR1-Adu. Furthermore, low-dose TfR1-Adu demonstrated greater capacity to reduce congophilic plaque burden. Collectively, these observations strongly support the applicability of TfR1-enabled BBB shuttle strategies to improve brain delivery and plaque-clearing efficacy while mitigating the risk of vascular-associated amyloid-related imaging abnormalities (ARIA) adverse effects associated with current Aβ immunotherapeutics.
Mission imputable: Effects of missing data processing on infectious disease detection and prognosis
Authors: Roy Suravi Saha , Nguyen Ngoc Thi , Zuniga Agustin , Sarhaddi Fatemeh , Lagerspetz Eemil , Flores Huber , Nurmi Petteri
Published: February 2025

Background

Missing data in medical datasets poses significant challenges for developing effective AI/ML pipelines. Inaccurate imputation can lead to biased results, reduced model performance, and compromised clinical insights. Understanding how different imputation methods affect AI/ML model performance is crucial for ensuring accurate clinical findings.

Objective

This study systematically investigates the effects of different imputation methods on AI/ML model performance and the clinical implications of these methods.

Methods

We investigate the impact of four different missing data strategies on the performance of common classification algorithms for analyzing medical data. The performance was evaluated based on sensitivity and specificity metrics for the tasks of predicting COVID-19 diagnosis and patient deterioration. We also perform feature analysis to understand the clinical implications the choice of imputation method has.

Results

Our findings show that the choice of imputation method significantly affects the performance of AI/ML techniques and the clinical conclusions drawn from the data. The optimal handling of missing values depends on (i) the composition of the features with missing values, (ii) the rate of missing values, and (iii) the pattern of the missing features. Using COVID-19 diagnosis and patient deterioration as representative examples of clinical tasks, our results indicate that MICE imputation yields the best overall performance, resulting in a 26% improvement in accuracy compared to baseline methods. Specifically, for predicting COVID-19 diagnosis, we achieved a sensitivity of 81% and specificity of 98%, while for patient deterioration, the sensitivity was 65% and specificity was 99%.

Conclusion

This study demonstrates the critical impact of missing data imputation on AI/ML model performance and the clinical insights derived from these models. Our findings underscore the importance of selecting appropriate imputation techniques tailored to the specific characteristics of medical data to ensure accurate and reliable AI/ML predictions.
Stability of emotional and behavioral problems in autistic children and adolescents during the COVID-19 pandemic
Authors: Boy Clemens , Truijens Femke L. , Louwerse Anneke , Visser Kirsten , Bastiaansen Dennis , Ester Wietske A. , Van Rijen Elisabeth H.M. , Van der Hallen Ruth , Dekker Linda P.
Published: February 2025

Purpose

The lasting impact of the COVID-19 pandemic on autistic children and adolescents remains uncertain. Disruptions to routines, social communication and support systems presented unique challenges. The existing body of research has produced inconclusive results, necessitating further investigation to elucidate this ambiguity. This study aims to provide clarity regarding the emotional and behavioral functioning of autistic youth in response to COVID-19 related lockdowns. We further explore distinct subgroups of Autism Spectrum Disorder (ASD), investigating the socially inflexible and demand avoidant profile.

Design/methodology/approach

To surpass short-term outcomes, this study examined emotional and behavioral problems (EBPs) by means of the Brief Problem Monitor in 69 autistic youth before, during and after a national lockdown in the Netherlands. Using individualized measurement (Reliable Change Indices), group-level changes were discerned. An exploratory analysis compared individuals from the socially inflexible and demand avoidant profile.

Findings

Both on a group and individual level, this findings suggest stability of EBPs in response to the COVID-19 pandemic and its corresponding measures. However, while the demand avoidant profile showed significantly more EBPs compared to the socially inflexible profile prior to the pandemic, the two profiles showed similar EBPs levels during and post-pandemic. Taken together, autistic youth and their families may have exhibited unique adaption strategies toward challenges caused by the pandemic and managed them better than initially expected.

Originality/value

The findings urge to look beyond group level functioning, and rather into nuances in ASD profiles to tailor interventions and support to the needs of autistic youth and families. A novelty of the study consists in having identified two different autism profiles to explain differences among subgroups of ASD.