bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke Complications in Patients Requiring Durable Mechanical Circulatory Support Systems After Extracorporeal Life Support
Authors: Saeed Diyar , Loforte Antonio , Morshuis Michiel , Schibilsky David , Zimpfer Daniel , Riebandt Julia , Pappalardo Federico , Attisani Matteo , Rinaldi Mauro , Haneya Assad , Ramjankhan Faiz , Donker Dirk W. , Jorde Ulrich P. , Pacini Davide , Otto Wolfgang , Stein Julia , Lewin Daniel , Jawad Khalil , Wieloch Radi , Ayala Rafael , Cremer Jochen , Borger Michael A. , Lichtenberg Artur , Gummert Jan , Potapov Evgenij ,   On behalf of Durable MCS after ECLS Study Group
Published: April 2022

Stroke is one of the leading complications following durable mechanical circulatory support (MCS) implantation. The aim of this multicenter study was to investigate stroke complications in patients requiring durable MCS following extracorporeal life support (ECLS). Data of 11 high volume MCS centers were collected and evaluated to identify patients who underwent durable MCS implantation after ECLS support between January 2010 and August 2018. The primary outcome was stroke following durable MCS implantation. Univariate and multivariate logistic regression analyses were performed to determine predictors of stroke. Overall, 531 patients met the inclusion criteria. Only patients who were supported with continuous flow pumps were included in this study accounting for 495 patients (median age 54 years old [interquartile range 47–60]). A total of 136 patients (27%) developed postoperative stroke on device during the follow-up (48% ischemic and 52% hemorrhagic) after a median durable MCS support of 320 [32–1,000] days, accounting for 0.17 events per patient-year. Of 133 patients with known date of stroke, a total of 47 (10%) developed stroke during the first 30 days (64% ischemic and 36% hemorrhagic), and 86 patients developed stroke after 30 days (38% ischemic and 62% hemorrhagic) of durable MCS support (late stroke). Survival rate was significantly lower in patients with hemorrhagic stroke (p = 0.00091). Stroke appears to be a common complication in patients transitioned to durable MCS support after ECLS. Hemorrhagic stroke is a more common type of late stroke and is associated with inferior outcomes.
Trends in Contemporary Use of Ventricular Assist Devices in Children Awaiting Heart Transplantation and Their Outcomes by Race/Ethnicity
Authors: Trivedi Jaimin , Slaughter Mark S. , Moskowitz William B. , Ghaleb Stephanie , Das Bibhuti B.
Published: April 2022

This retrospective study included children aged ≤18 years who had durable ventricular assist devices (VADs) as a bridge to transplantation from the United Network Organ Sharing (UNOS) database between 2011 and 2020. We evaluated 90 day waitlist mortality and 1 year posttransplant mortality after VAD implantation in children stratified by race/ethnicity: Black, White, and Others. The VAD was used in a higher proportion of Black children listed for heart transplantation (HT) (26%) versus Other (25%) versus White (22%); p < 0.01. Black children had Medicaid health insurance coverage (67%) predominantly at the time of listing for HT. There was no significant overall difference in waitlist survival among the three groups supported with VAD at the time of listing (log-rank p = 0.4). On the other hand, the 90 day waitlist mortality after the VAD implantation at listing and while listed was the lowest among Black (6%) compared with White (13%) and Other (14%) (p < 0.01). The multivariate regression analysis showed that Other race (hazard ratio [HR], 2.29; p < 0.01), Black race (HR, 2.13; p < 0.01), use of mechanical ventilation (HR, 1.72; p = 0.01), and Medicaid insurance (HR, 1.54; p = 0.04) were independently associated with increased 1 year posttransplant mortality. In conclusion, Black children had more access to durable VAD support than White children. The 90 day waitlist mortality was significantly lower in Black children compared with White and Other after VAD implantation. However, Black and Other racial/ethnic children with VAD at transplant had higher 1 year posttransplant mortality than White children. Future studies to elucidate the reasons for these disparities are needed.
Successful Explantation of Berlin Heart Excor in Two Young Children
Authors: Torpoco Rivera Diana Milagros , Schneider Jordan , Lawrence David , Dentel John , Sehgal Swati
Published: April 2022

Berlin Heart EXCOR ventricular assist device (VAD) implantation in children is widely used as bridge-to-heart transplantation. Berlin left ventricular assist device (LVAD) support as a bridge to recovery is rare. There is a scarcity of literature describing systematic evaluation in pediatric VAD explantation. Patient 1. A 3 month old boy presented with acute heart failure secondary to myocarditis. An echocardiogram demonstrated severely depressed left ventricular function. He required ECMO cannulation and was decannulated 11 days later. He continued to be hemodynamically unstable and required Berlin LVAD implantation with the intent to bridge to transplantation. Patient 2. A 3 month old boy presented initially with a heart rate of 250 beats/min and an electrocardiogram showed multifocal atrial tachycardia. An echocardiogram showed severely decreased left ventricular function. He was placed on ECMO due to unstable hemodynamics. He did not tolerate ECMO decannulation due to persistent chaotic atrial rhythm and underwent Berlin LVAD implantation with the intent to bridge to transplantation. After both patients showed evidence of myocardial recovery, they underwent a weaning protocol that includes: screening, trial-off with echocardiography, and trial-off in the catheterization suite. Our patients met the criteria and underwent successful explantation. Explantation of VAD can be successfully performed even in young children with appropriate candidate selection and a multidisciplinary and systematic approach.
Thoracoabdominal Normothermic Regional Perfusion for Cardiac Procurement
Authors: Joyce David L. , Carlson Samuel F. , Kohmoto Takushi , Durham Lucian , Ubert Adam , Candek Christopher , Koerten David , Joyce Lyle D.
Published: April 2022

In donation after circulatory death donors, warm ischemia time is a significant threat to successful cardiac transplantation. The ability to perfuse these organs during the minutes after death, until cardiac evaluation is completed to satisfaction, is crucial in limiting total warm ischemic time. Thoracoabdominal normothermic regional perfusion (TANRP) has emerged as a promising strategy for recovering and monitoring these hearts. We propose a series of clinical practice pearls that we follow for all donation after circulatory death procurements to streamline the process of setting up a TANRP circuit and ensuring all team members present at time procurement are familiar with the procedure. Bicaval cannulation is achieved via the abdomen for aortic cannulation, and via the chest for right atrial cannulation, avoiding deairing maneuvers and providing the shortest possible duration from incision to initiation of cardiopulmonary bypass. Here, we describe a series of practice techniques which we have utilized in our early experience with TANRP.
Mat Pilates training and blood pressure reactivity responses to psychological stress: comparison between normotensive and hypertensive postmenopausal women
Authors: Gonçalves Ludimila Ferreira , Batista Jaqueline Pontes , Tavares Julia Buiatte , de Souza Tállita Cristina Ferreira , Mariano Igor Moraes , Amaral Ana Luiza , Rodrigues Mateus de Lima , Puga Guilherme Morais
Published: April 2022

Objectives

The aim of this study is to compare resting blood pressure and blood pressure reactivity responses to psychological stress in normotensive and hypertensive postmenopausal women after 12 weeks of Mat Pilates training.

Methods

Twenty-three hypertensive and 24 normotensive postmenopausal women, performed Mat Pilates training 3× a week for 12 weeks. Before and after the intervention, resting blood pressure, heart rate, and blood pressure reactivity to psychological stress through the electronic version of Stroop test protocol (3 minutes) were measured. We calculated the variation (Δ) of blood pressure (peak of blood pressure during the Stroop stress test minus resting blood pressure before test).

Results

The two-way ANOVA showed that the Δ of systolic blood pressure, diastolic blood pressure, and the mean blood pressure was reduced (P < 0.05) after training only in the hypertensive. The resting systolic, diastolic, and mean blood pressures decreased by (P < 0.05) over time in both groups with no interaction or difference.

Conclusion

Mat Pilates was able to reduce resting blood pressure in both hypertensive and normotensive, and blood pressure reactivity after psychological stress in hypertensive but not in normotensive postmenopausal women.
Pulmonary perfusion imaging and delayed imaging to measure pulmonary capillary permeability in pulmonary contusion
Authors: Xiong Kai , Li Shicong , Yu Yao , Duan Shuning , Zhang Peng , Wang Peng , Li Xin , Chen Yuan , Cui Yuantao , Wang Yuanguo , Shen Yiming , Yang Zhaoyu , Lu Chao , Tao Ziyou , Liu Yuxin , Zhang Peng , Meng Zhaowei
Published: April 2022

Purpose

Explore the application value of pulmonary perfusion imaging and delayed imaging for evaluating pulmonary capillary permeability.

Materials and methods

After establishing a rat model of pulmonary contusion, changes in the metabolic index of technetium-99m macroaggregated albumin (99mTC-MAA) in the lungs of model rats were evaluated for two consecutive days. 99mTC-MAA metabolic indices of rat lungs with pulmonary contusion of varying severity (mild, moderate, and severe) were correlated with lung wet/dry weight ratio (W/D) and Evans blue extravasation. Finally, the method was validated in patients with pulmonary contusion and one healthy volunteer.

Results

The 99mTC-MAA metabolic index was 23.56% ± 2.44% in healthy control (HC) rat lung, 8.56% ± 3.42% immediately after lung contusion (d0), 8.35% ± 3.20% after 1 day (d1), and 17.45% ± 6.44% after 2 days (d2); indices at d0 and d1 were significantly higher than those at HC (P < 0.05). The metabolic index of 99mTC-MAA in lung had significant negative correlations with W/D (r = −0.8025; P = 0.0092) and Evans blue extravasation (r = −0.9356; P = 0.0002). Metabolic and oxygenation indices of 99mTC-MAA exhibited a significant positive linear correlation in patients with pulmonary contusion (r = 0.8925; P = 0.0416).

Conclusion

Pulmonary perfusion and delayed imaging of 99mTC-MAA have potential value for evaluating pulmonary capillary permeability.
Effectiveness of aquatic exercise in lower limb osteoarthritis: a meta-analysis of randomized controlled trials
Authors: Duan Xiaodong , Wei Wei , Zhou Ping , Liu Xi , Yu Jihua , Xu Yang , Huang Liheng , Yang Shibin
Published: April 2022

The objective of this study was to evaluate the short-term and follow-up effectiveness of aquatic training on the health status of lower limb osteoarthritis. Randomized controlled trials (RCTs) on related topics were systematically searched in PubMed, Embase, Web of Science, the Cochrane Library, Physiotherapy Evidence Database (PEDro), the China National Knowledge Infrastructure and Wanfang databases from inception to January 2021. RevMan 5.3 was used for statistical analysis, and the standardized mean difference (SMD) was used to present pooled effect sizes. As a result, 19 RCTs (1592 patients) were included. Compared with unsupervised home exercise or usual care (land-based training excluded), aquatic training showed short-term pain relief (SMD, −0.54; 95% CI, −0.81 to −0.28), physical function improvement (SMD, −0.64; 95% CI, −1.00 to −0.28), stiffness reduction (SMD, −0.40; 95% CI, −0.79 to −0.01) and improved function in sport and recreation (SMD, −0.30; 95% CI, −0.59 to −0.02). Analyses restricted to patients with knee osteoarthritis only also confirmed the positive effects of aquatic training on most dimensions excluding physical function. At medium-term follow-ups, improvements in physical function and function in sport and recreation were observed. No significant difference was observed between arms in the above four outcomes at long-term follow-ups. All studies reported no major adverse event with relation to aquatic training, and the minor adverse events were not common. It is concluded that aquatic training likely has short-term benefits on pain, physical function, stiffness and sport ability in lower limb osteoarthritis patients, but these positive effects may not last long.
The Acceptability and Feasibility of Routine Use of Validated Cancer Symptom Assessment Instruments Among Patients and Nurses in the Oncology Ward at Princess Marina Hospital, in Gaborone, Botswana
Authors: Swart Norman Carl , Zhang Amy , Lazenby Mark
Published: April 2022

This cross-sectional study evaluated the acceptability and feasibility of oncology nurses using validated cancer symptom assessment instruments to assess symptom burden. A consecutive sample of cancer patients and oncology ward nurses at a hospital in Gaborone, Botswana, was used. Patients' symptom burden was assessed using the Memorial Symptom Assessment Scale–Short Form and the Visual Analog Scale-Pain, and patient- and nurse-acceptability data were assessed using the Client Satisfaction Questionnaire and the Intervention Rating Profile. Rates of participation, assessment length of time, and rates of completed Memorial Symptom Assessment Scale–Short Form and Visual Analog Scale-Pain determined feasibility. The sample included 124 patients (female, 84) and 20 nurses (female, 14). The mean (SD) Client Satisfaction Questionnaire score was 30.1 (2.8; minimum-maximum, 19-32), and the mean (SD) Intervention Rating Profile score was 86.8 (4.3; minimum-maximum, 74-90). There was a significant difference in the scores of the Intervention Rating Profile between preassessment (mean [SD], 80.1 [6.0]) and postassessment (mean [SD], 86.8 [4.3]; t
19 = −4.853, P < .001). All patient participants (100%) completed assessments. The routine nursing assessment was acceptable to and feasible among patients and nurses. Nurses can integrate validated instruments into routine nursing assessment to determine patients' symptom burden for quick referrals to palliative care.
Induced membrane technique for acute bone loss and nonunion management of the tibia
Authors: Chloros George D. , Kanakaris Nikolaos K. , Harwood Paul J. , Giannoudis Peter V.
Published: April 2022

Objectives:

To report our experience and clinical results of using the Masquelet technique for the treatment of tibial nonunions and acute traumatic tibial bone defects.

Design:

Retrospective study of prospectively collected data (Level IV).

Setting:

Level I trauma center in the UK.

Patients/Participants:

Consecutive patients with tibial nonunions and open fractures associated with bone loss.

Intervention: Two-stage Masquelet Procedure for the tibia.

Main Outcome Measurements:

Clinical and imaging assessment at 6 weeks, 3,6,9,12 months, or until pain-free mobilization and union.

Results:

There were 17 eligible patients, with a mean size of bone defect of 6 cm (range, 4–8 cm) and an 88.2% union rate at a mean of 8 months (range 5–18 months). Mean range of motion was 95 degrees of knee flexion (range 80°–130°). All patients but 2 returned to their previous occupation.

Conclusions:

The Masquelet technique is simple, effective, and has a high rate of success for the management of a variety of situations including acute bone loss or infected nonunions and is associated with a low incidence of complications.
Sensors and digital medicine in orthopaedic surgery
Authors: Merle Géraldine , Parent-Harvey Alexandre , Harvey Edward J.
Published: April 2022

Digital health principles are starting to be evident in medicine. Orthopaedic trauma surgery is also being impacted —indirectly by all other improvements in the health ecosystem but also in particular efforts aimed at trauma surgery. Data acquisition is changing how evidence is gathered and utilized. Sensors are the pen and paper of the next wave of data acquisition. Sensors are gathering wide arrays of information to facilitate digital health relevance and adoption. Early adaption of sensor technology by the nonlegacy health environment is what has made sensor driven data acquisition so palatable to the normal health care system. As it applies to orthopaedic trauma, current sensor driven diagnostics and surveillance are nowhere near as developed as in the larger medical community. Digital health is being explored for health care records, data acquisition in diagnostics and rehabilitation, wellness to health care translation, intraoperative monitoring, surgical technique improvement, as well as some early-stage projects in long-term monitoring with implantable devices. The internet of things is the next digital wave that will undoubtedly affect medicine and orthopaedics. Internet of things (loT) devices are now being used to enable remote health monitoring and emergency notification systems. This article reviews current and future concepts in digital health that will impact trauma care.
Assessing the Impact of Nasotracheal Intubation on Postoperative Neonates With Congenital Heart Disease: A Quality Improvement Project at a Single Heart Center
Authors: Marietta Jennifer , Glotzbach Kristi L. , Jones Courtney E. , Ou Zhining , Profsky Tiffany K. , Clegg Dave , Winder Melissa M. , Pribble Charles G.
Published: April 2022

OBJECTIVES:

Nasotracheal intubation (NTI) is associated with fewer unplanned extubations and improved oral motor skills compared with orotracheal intubation (OTI). Our study aimed to implement a practice change from OTI to NTI for neonatal cardiac surgery and assess impact on postoperative outcomes.

DESIGN:

Single-center, prospective, quality improvement study.

SETTING:

Academic children’s hospital.

PATIENTS:

One hundred thirty neonates undergoing cardiac surgery with cardiopulmonary bypass.

INTERVENTIONS:

NTI during index cardiac surgery.

MEASUREMENTS AND MAIN RESULTS:

Data were collected between January 2019 and April 2021. The study was implemented in three phases: retrospective: OTI neonates (n = 43), I: safety and feasibility of NTI (n = 17), and II: speech language pathology (SLP) evaluation on postoperative day 1 facilitated by NTI (n = 70). Retrospective and phase I patients were combined for analysis. Groups were compared using Kruskal-Wallis test or Wilcoxon rank-sum test.

Ninety-one percent of eligible neonates were nasotracheally intubated. There were no clinically significant complications. Days to first SLP encounter decreased from a median 4.5 days (interquartile range [IQR], 3.8–6.2) to 1.1 days (IQR, 1.0–1.9; p < 0.001). Oral readiness time decreased from a median of 6.6 days (IQR, 5.4–8.9) to 4.3 days (IQR, 3.4–8.6; p < 0.001). 

CONCLUSIONS:

NTI is feasible and safe in neonatal cardiac surgery. System-level engagement with stakeholders is necessary to change clinical practice. NTI facilitates early SLP evaluation and treatment and significantly affects oral readiness after neonatal cardiac surgery.
Developing Complex, Cross-Cutting Skills in the Public Health Workforce: Using a Crosswalk Analysis to Map Public Health Competencies to Strategic Skills for the Governmental Public Health Workforce
Authors: Amos Kathleen , Levy Nicole A. , Bialek Ron , Arana Mayela , Murrman Marita
Published: April 2022

In recent years, many public health organizations have used 2 frameworks for workforce development planning and action: the Core Competencies for Public Health Professionals (Core Competencies) and the Strategic Skills for the Governmental Public Health Workforce (Strategic Skills). A third framework is also available for organizations emphasizing population health: the Competencies for Population Health Professionals (Population Health Competencies). This crosswalk analysis—conducted by the Public Health Foundation with input from the Region 2 Public Health Training Center and the de Beaumont Foundation—harmonizes these 3 schemas by systematically mapping the 2014 version of the Core Competencies and the 2019 Population Health Competencies with the 2017 version of the Strategic Skills to produce a comprehensive matrix depicting their relationships. When developing training and curricula, health department personnel and academic faculty can use the results to identify competencies public health professionals may wish to master to build the Strategic Skills. Organizations can also replicate the analytic methodology to align the Core Competencies with other sets of strategic priorities.
Contrast Media Reduction in Computed Tomography With Deep Learning Using a Generative Adversarial Network in an Experimental Animal Study
Authors: Haubold Johannes , Jost Gregor , Theysohn Jens Matthias , Ludwig Johannes Maximilian , Li Yan , Kleesiek Jens , Schaarschmidt Benedikt Michael , Forsting Michael , Nensa Felix , Pietsch Hubertus , Hosch René
Published: April 2022

Objective

This feasibility study aimed to use optimized virtual contrast enhancement through generative adversarial networks (GAN) to reduce the dose of iodine-based contrast medium (CM) during abdominal computed tomography (CT) in a large animal model.

Methods

Multiphasic abdominal low-kilovolt CTs (90 kV) with low (low CM, 105 mgl/kg) and normal contrast media doses (normal CM, 350 mgl/kg) were performed with 20 healthy Göttingen minipigs on 3 separate occasions for a total of 120 examinations. These included an early arterial, late arterial, portal venous, and venous contrast phase. One animal had to be excluded because of incomplete examinations. Three of the 19 animals were randomly selected and withheld for validation (18 studies). Subsequently, the GAN was trained for image-to-image conversion from low CM to normal CM (virtual CM) with the remaining 16 animals (96 examinations). For validation, region of interest measurements were performed in the abdominal aorta, inferior vena cava, portal vein, liver parenchyma, and autochthonous back muscles, and the contrast-to-noise ratio (CNR) was calculated. In addition, the normal CM and virtual CM data were presented in a visual Turing test to 3 radiology consultants. On the one hand, they had to decide which images were derived from the normal CM examination. On the other hand, they had to evaluate whether both images are pathological consistent.

Results

Average vascular CNR (low CM 6.9 ± 7.0 vs virtual CM 28.7 ± 23.8, P < 0.0001) and parenchymal (low CM 1.5 ± 0.7 vs virtual CM 3.8 ± 2.0, P < 0.0001) CNR increased significantly by GAN-based contrast enhancement in all contrast phases and was not significantly different from normal CM examinations (vascular: virtual CM 28.7 ± 23.8 vs normal CM 34.2 ± 28.8; parenchymal: virtual CM 3.8 ± 2.0 vs normal CM 3.7 ± 2.6). During the visual Turing testing, the radiology consultants reported that images from normal CM and virtual CM were pathologically consistent in median in 96.5% of the examinations. Furthermore, it was possible for the examiners to identify the normal CM data as such in median in 91% of the cases.

Conclusions

In this feasibility study, it could be demonstrated in an experimental setting with healthy Göttingen minipigs that the amount of CM for abdominal CT can be reduced by approximately 70% by GAN-based contrast enhancement with satisfactory image quality.
Interobserver Agreement Rates on Fibroblast Activation Protein Inhibitor–Directed Molecular Imaging and Therapy
Authors: Serfling Sebastian E. , Hartrampf Philipp E. , Zhi Yingjun , Higuchi Takahiro , Rowe Steven P. , Bundschuh Lena , Essler Markus , Buck Andreas K. , Bundschuh Ralph Alexander , Werner Rudolf A.
Published: April 2022

Objectives

Fibroblast activation protein (FAP) has emerged as a novel target for FAP inhibitor (FAPI)–directed molecular imaging and endoradiotherapy (ERT). We aimed to assess the interobserver agreement rates for interpretation of 68Ga-FAPI-4 PET/CT and decision for ERT.

Patients and Methods

A random order of 68Ga-FAPI-4 PET/CTs from 49 oncology patients were independently interpreted by 4 blinded readers. Per scan, visual assessment was performed, including overall scan impression, number of organ/lymph node (LN) metastases, and number of affected organs/LN regions. Moreover, a maximum of 3 target lesions, defined as largest in size and/or most intense, per organ compartment were identified, which allowed for an additional quantitative interobserver assessment of LN and organ lesions. To investigate potential reference tissues, quantification also included unaffected liver parenchyma and blood pool. Readers also had to indicate whether FAPI-directed ERT should be considered (based on intensity of uptake and widespread disease). Interobserver agreement rates were evaluated using intraclass correlation coefficients (ICCs) and interpreted according to Cicchetti (with 0.4–0.59 indicating fair, and 0.6–0.74 good, agreement).

Results

On a visual basis, the agreement rate for an overall scan impression was fair (ICC, 0.42; 95% confidence interval [CI], 0.27–0.57). The concordance rate for number of affected LN areas was also fair (ICC, 0.59; 95% CI, 0.45–0.72), whereas the number of LN metastases, number of affected organs, and number of organ metastases achieved good agreement rates (ICC, ≥0.63). In a quantitative analysis, concordance rates for LN were good (ICC, 0.70; 0.48–0.88), but only fair for organ lesions (ICC, 0.43; 0.26–0.60). In regards to background tissues, ICCs were good for unaffected liver parenchyma (0.68; 0.54–0.79) and fair for blood pool (0.43; 0.29–0.58). When readers should decide on ERT, concordance rates were also fair (ICC, 0.59; 95% CI, 0.46–0.73).

Conclusions

For FAPI-directed molecular imaging and therapy, a fair to good interobserver agreement rate was achieved, supporting the adoption of this radiotracer for clinical routine and multicenter trials.
Superiority of 11C-Choline PET/CT in the Delineation of a Rare Intracranial Diffuse Embryonic Tumor
Authors: Dong Ye , Zhou Wenlan , Han Yanjiang , Wu Hubing
Published: April 2022

Intracranial diffuse embryonal tumor in the adult is rare. We report a young woman with a diffuse embryonal malignancy in the saddle area, which was depicted well by 11C-choline PET/CT, superior to 18F-FDG PET/CT and contrast-enhanced MRI. Under the guiding of 11C-choline PET/CT, the biopsy was successfully performed and the diagnosis was established. This case highlights that11C-chione PET/CT may be useful to diagnose and delineate the intracranial diffuse embryonic tumors.
Prostate-Specific Membrane Antigen–Avid Bone Metastases From Urothelial Carcinoma of the Bladder
Authors: Zhao Bo , Dong Aisheng , Zuo Changjing
Published: April 2022

Prostate-specific membrane antigen (PSMA) PET findings of urothelial carcinoma were rarely reported. We describe 18F-FDG PET/CT and 68Ga-PSMA-11 PET/MRI findings in a case of urothelial carcinoma of the bladder with bone metastases in the sternum, ribs, spine, pelvis, and femurs. The bone metastases showed isodensity to hyperdensity and mild to intense FDG uptake on FDG PET/CT and moderate to intense PSMA uptake on PSMA PET/MRI. PSMA PET/MRI more clearly delineated the bone metastases compared with FDG PET/CT.
Review of the Sonographic Features of Interpectoral (Rotter) Lymph Nodes in Breast Cancer Staging
Authors: Engel Adam J. , Shin Kyungmin , Adrada Beatriz E. , Moseley Tanya W. , Krishnamurthy Savitri , Whitman Gary J.
Published: April 2022

This article reviews the ultrasound evaluation and staging of breast cancer with respect to the involvement of interpectoral (Rotter) lymph nodes. The primary objective is to demonstrate and assess the characteristic sonographic findings of interpectoral (Rotter) lymph nodes to help provide accurate nodal staging information. We aim to provide a comprehensive review and serve as an imaging guide for the identification and evaluation of Rotter lymph nodes. The detection of abnormalities and pathologic features of metastatic axillary nodal disease in the interpectoral region is reviewed, and the impact on clinical management and treatment is discussed. In the radiology literature, there is no comprehensive review of the sonographic appearance and evaluation of Rotter lymph nodes.
Role Clarity and Interprofessional Colleagues in Psychological Safety
Authors: Klenke-Borgmann Laura , DiGregorio Heiddy , Cantrell Mary Ann
Published: April 2022

Summary Statement

Psychological safety in high-fidelity simulation-based experiences ensures that learners feel safe with new experiences in the service of learning. This article is a faculty reflection on breaches in the psychological safety among nursing students in 2 independent, high-fidelity simulation-based experience studies that were conducted in 2019. Demonstrated breaches in psychological safety included fear and anxiety in the sole provider role in multiple-patient simulations and incivility directed toward nursing students in a primary nurse role in interprofessional simulations. This article adds to the growing literature on psychological safety by sharing important lessons learned regarding role clarity and interprofessional colleagues, proposing recommendations, and providing suggestions for future research on psychological safety.
A retrospective cross-sectional analysis of community perceptions of flu and COVID-19 vaccines at Turtle Creek Primary Care Center
Authors: Murali Anjana , Sojati Jorna , Levochkina Marina , Pressimone Catherine , Griffith Kobi , Fan Erica , Dakroub Allie
Published: April 2022

Background

Influenza (flu) and COVID-19 vaccination rates are subpar across the US, especially in racial and/or socioeconomic minority groups who are understudied in public health literature.

Objective

The objective of this study was to elucidate the attitudes of Turtle Creek patients towards flu and COVID-19 vaccines, with the goal of establishing targetable vaccine education gaps and ultimately increasing vaccine uptake in the community.

Design/Patients

This study was conducted as a retrospective cross-sectional analysis. Authors completed 123 patient phone surveys of patients cared for at the Turtle Creek Primary Care Center inquiring about flu and COVID-19 infection status and vaccination uptake (August 26 - October 10, 2021).

Approach/Key Results

Our data revealed a significant association between COVID-19 and flu vaccine acceptance. Additionally, we found a strong association between vaccine acceptance and age, with older patients being more likely to be vaccinated against COVID-19. Using multivariable logistic regression models, we assessed how flu and COVID-19 vaccine acceptance was affected by informational sources participants trusted most. In the COVID-19 models, those who cited “trusting medical professionals” had higher odds of vaccine acceptance while participants who cited “trusting social media” had significantly decreased odds of vaccine acceptance.

Conclusion

Our study revealed significant trends for flu and COVID-19 vaccine acceptance by sociodemographic factors and trust in the medical system. Using these data, we can create future interventions to overcome vaccine hesitancy.
Development of a Highly Sensitive Serum Neurofilament Light Chain Assay on an Automated Immunoassay Platform
Authors: Lee Stephen , Plavina Tatiana , Singh Carol M , Xiong Kuangnan , Qiu Xiaolei , Rudick Richard A , Calabresi Peter A , Stevenson Lauren , Graham Danielle , Raitcheva Denitza , Green Christopher , Matias Madeleine , Uzgiris Arejas J
Published: April 2022

Background

Neurofilament light chain (NfL) is an axonal cytoskeletal protein that is released into the extracellular space following neuronal or axonal injury associated with neurological conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and other diseases. NfL is detectable in cerebrospinal fluid (CSF) and blood. Numerous studies in MS have demonstrated that NfL correlates with disease activity, predicts disease progression, and is reduced by treatment with MS disease-modifying drugs, making NfL an attractive candidate to supplement existing clinical and imaging measures in MS. However, for NfL to achieve its potential as a clinically useful biomarker for clinical decision-making or drug development, a standardized, practical, widely accessible assay is needed. Our objective was to validate the analytical performance of the novel serum neurofilament light (sNfl) assay on the ADVIA Centaur® XP immunoassay system.

Methods

The research assay was evaluated on the ADVIA Centaur XP immunoassay system from Siemens Healthineers. The lower limit of quantitation (LLoQ), intra-assay variation, assay range, cross-reactivity with neurofilament medium and heavy chains, and effect of interfering substances were determined. NfL assay values in serum and CSF were compared with radiological and clinical disease activity measures in patients with MS and ALS, respectively. This assay was further optimized to utilize serum, plasma, and CSF sample types and transferred to Siemens’ CLIA laboratory, where it was analytically validated as a laboratory-developed test.

Results

In this study, a LLoQ of 1.85 pg/mL, intra-assay variation of <6%, and an assay range of up to 646 pg/mL were demonstrated. A cross-reactivity of <0.7% with neurofilament medium and heavy chains was observed, and the assay was not significantly affected by various interfering substances encountered in clinical specimens. Serum and CSF NfL assay values were associated with radiological and clinical disease activity measures in patients with MS and ALS, respectively.

Conclusion

The analytical performance of the NfL assay fulfilled all acceptance criteria; therefore, we believe the assay is acceptable for use in both research and clinical practice settings to determine elevated sNfL levels in patients.
In vitro and in vivo antioxidant therapeutic evaluation of Dodonaea viscosa Jacq.
Authors: Khan Siraj , Rehman Mujeeb Ur , Khan Muhammad Zafar Irshad , Muhammad Khan , Haq Ihsan Ul , Khan Muhammad Ijaz
Published: April 2022

Context

Natural antioxidants are vital to promote health and treat critical diseased conditions in the modern healthcare system.

Objective

This work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV).

Material and methods

The aqueous extract of leaves and seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H2O2) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities.

Results

Seeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with AgI and HgII show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control.

Discussion and Conclusion

The crude aqueous extracts of leaves and seeds of plant DV show promising antioxidant potential both in in vitro and in vivo evaluation.
A Mixed Methods Study Evaluating Acceptability of a Daily COVID-19 Testing Regimen with a Mobile-App Connected, At-Home, Rapid Antigen Test: Implications for Current and Future Pandemics
Authors: Nguyen Nadia , Lane Benjamin , Lee Sangwon , Gorman Sharon Lipsky , Wu Yumeng , Li Alicia , Lu Helen , Elhadad Noemie , Yin Michael , Meyers Kathrine
Published: April 2022

Background

Widespread use of at-home rapid COVID-19 antigen tests has been proposed as an important public health intervention to interrupt chains of transmission. Antigen tests may be preferred over PCR because they provide on-demand results for relatively low cost and can identify people when they are most likely to be infectious, particularly when used daily. Yet the extent to which a frequent antigen testing intervention will result in a positive public health impact for COVID-19 will depend on high acceptability and high adherence to such regimens.

Methods

We conducted a mixed-methods study assessing acceptability of and adherence to a daily at-home mobile-app connected rapid antigen testing regimen among employees of a US-based media company. Acceptability was assessed across seven domains of the Theoretical Framework of Acceptability.

Results

Among 31 study participants, acceptability of the daily testing intervention was generally high, with participants reporting high perceived effectiveness, intervention coherence, and self-efficacy; positive affective attitude; acceptable degree of burden and opportunity cost; and assessing the intervention as ethical. 71% reported a preference to test daily using an at-home antigen test than weekly employment-based PCR. Mean adherence to the 21-day testing regimen was 88% with 43% of participants achieving 100% adherence, 48% testing at least every other day, and 10% testing less than every other day.

Conclusions

Despite overall high acceptability and adherence, we identified three implementation challenges that must be addressed for frequent serial testing for COVID-19 to be implemented at scale and have a positive public health impact. First, users need guidance on how and when to adapt testing frequencies to different epidemiological conditions. Second, users and institutions need guidelines for how to safely store and share test results. Third, implementation of serial testing strategies must prioritize health equity and protect those most vulnerable to COVID-19.
Redox regulation of the SARS-CoV-2 main protease provides new opportunities for drug design
Authors: Funk Lisa-Marie , Poschmann Gereon , Chari Ashwin , von Pappenheim Fabian Rabe , Stegmann Kim-Maren , Dickmanns Antje , Eulig Nora , Wensien Marie , Paknia Elham , Heyne Gabi , Penka Elke , Pearson Arwen R. , Berndt Carsten , Fritz Tobias , Bazzi Sophia , Uranga Jon , Mata Ricardo A. , Dobbelstein Matthias , Hilgenfeld Rolf , Curth Ute , Tittmann Kai
Published: April 2022

Abstract

Besides vaccines, the development of antiviral drugs targeting SARS-CoV-2 is critical for stopping the current COVID-19 pandemic and preventing future outbreaks. The SARS-CoV-2 main protease (Mpro), a cysteine protease with essential functions in viral replication, has been validated as an effective drug target. Here, we show that Mpro is subject to redox regulation and reversibly switches between the enzymatically active dimer and the functionally dormant monomer through redox modifications of cysteine residues. These include sulfenylation, disulfide formation between the catalytic cysteine and a proximal cysteine, and generation of an allosteric lysine-cysteine SONOS bridge that is required for structural stability under oxidative stress conditions, such as those exerted by the innate immune system. We identify homo- and heterobifunctional reagents that mimic the redox switching and possess antiviral activity. The discovered redox switches are conserved in main proteases from other coronaviruses, e.g. MERS and SARS-CoV, indicating their potential as common druggable sites.
Functional Recovery from Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts is Dependent on Neurite Outgrowth
Authors: Hills Rachel , Mossman Jim A. , Bratt-Leal Andres M. , Tran Ha , Williams Roy M. , Stouffer David G. , Sokolova Irina V. , Sanna Pietro P. , Loring Jeanne F. , Lelos Mariah J.
Published: April 2022

Transplantation of human pluripotent stem cell-derived dopaminergic (DA) neurons is an emerging therapeutic strategy for Parkinson’s disease (PD). In this study, we demonstrate, for the first time, that that functional recovery after DA neuron transplant is critically dependent on graft-host integration, and not dependent on graft size or DA neuron content. Specifically, in anticipation of an autologous DA neuron transplant strategy, we studied two human induced pluripotent stem cell lines derived from people with idiopathic PD. We confirmed the cells’ ability to differentiate into mature DA neurons in vitro by assessing electrophysiology and depolarization-induced neurotransmitter release. To evaluate efficacy, we transplanted DA neuron precursors into a hemiparkinsonian rat model. We differentiated the cell lines for either 18 (d18) or 25 days (d25) to investigate the effect of cell maturity on efficacy. We found comparable graft survival in d18 and d25 groups from both cell lines, but behavioral analysis revealed that only d18 preparations, from both cell lines, resulted in recovery of motor impairments. Immunohistochemical analysis did not reveal any DA neuron-associated markers that correlated with efficacy. However, we found striking and consistent differences in graft neurite outgrowth between the two culture timepoints. The functional grafts from d18 cells had more outgrowth than non-functional d25 grafts. A time course of gene expression during differentiation of the cell lines revealed differences in genes associated with DA neuron development and neurite plasticity. These results are the first to demonstrate that graft-host integration, and not DA neuron content, is key to graft-induced functional recovery. The gene expression profiling may offer insight into the optimal developmental stage for graft efficacy.
Female behavior drives the formation of distinct social structures in C57BL/6J versus wild-derived outbred mice in field enclosures
Authors: Vogt Caleb C. , Zipple Matthew N. , Sprockett Daniel D. , Miller Caitlin H. , Hardy Summer X. , Arthur Matthew K. , Greenstein Adam M. , Colvin Melanie S. , Michel Lucie M. , Moeller Andrew H. , Sheehan Michael J.
Published: April 2022

Social behavior and social organization have major influences on individual health and fitness. Yet, biomedical research focuses on studying a few genotypes under impoverished social conditions. Understanding how lab conditions have modified social organizations of model organisms, such as lab mice, relative to natural populations is a missing link between socioecology and biomedical science. Using a common garden design, we describe the formation of social structure in the well-studied laboratory mouse strain, C57BL/6J, in replicated mixed-sex populations over 10-day trials compared to control trials with wild-derived outbred house mice in outdoor field enclosures. We focus on three key features of mouse social systems: (i) territory establishment in males, (ii) female social relationships, and (iii) the social networks formed by the populations. Male territorial behaviors were similar but muted in C57 compared to wild-derived mice. Female C57 sharply differed from wild-derived females, showing little social bias toward cage mates and exploring substantially more of the enclosures compared to all other groups. Female behavior consistently generated denser social networks in C57 than in wild-derived mice. The repeatable societies formed under field conditions highlights opportunities to experimentally study the interplay between society and individual biology using model organisms.
Clonal spreading of tumor-infiltrating T cells underlies the robust antitumor immune responses
Authors: Aoki Hiroyasu , Tsunoda Mikiya , Ogiwara Haru , Shimizu Haruka , Abe Haruka , Abe Takaya , Shichino Shigeyuki , Matsushima Kouji , Ueha Satoshi
Published: April 2022

The repertoire of tumor-infiltrating T cells is an emerging perspective for characterizing effective antitumor T-cell responses. Oligoclonal expansion of tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrated that the polyclonal fraction of the tumor-reactive T-cell repertoire consisting of relatively minor clones increased in tumor-bearing mice treated with anti-PD-L1 or anti-CD4 monoclonal antibody, which was correlated with antitumor effect. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7+ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones (“clonal spreading”) is an important mechanism by which anti-PD-L1 and anti-CD4 treatments induce robust and durable antitumor T-cell responses.
Effects of abiotic environment on invertebrate herbivory depend on plant community context in a montane grassland
Authors: Halliday Fletcher W. , Cappelli Seraina L , Laine Anna-Liisa
Published: April 2022

Invertebrate herbivores are important and diverse, and their abundance and impacts are expected to undergo unprecedented shifts under climate change. Yet, past studies of invertebrate herbivory have documented a wide variety of responses to changing temperature, making it challenging to predict the direction and magnitude of these shifts. One explanation for these idiosyncratic responses is that changing environmental conditions may drive concurrent changes in plant communities and herbivore traits. Thus, the impacts of changing temperature on herbivory might depend on how temperature combines and interacts with characteristics of plant communities and the herbivores that occupy them. Here, we test this hypothesis by surveying invertebrate herbivory in 220, 0.5 meter-diameter herbaceous plant communities along a 1101-meter elevational gradient. Our results suggest that increasing temperature can drive community-level herbivory via at least three overlapping mechanisms: increasing temperature directly reduced herbivory, indirectly affected herbivory by reducing phylogenetic diversity of the plant community, and indirectly affected herbivory by altering the effects of functional and phylogenetic diversity on herbivory. Consequently, increasing functional diversity of plant communities had a negative effect on herbivory, but only in colder environments while a positive effect of increasing phylogenetic diversity was observed in warmer environments. Moreover, accounting for differences among herbivore feeding guilds considerably improved model fit, because different herbivore feeding guilds varied in their response to temperature and plant community composition. Together, these results highlight the importance of considering both plant and herbivore community context in order to predict how climate change will alter invertebrate herbivory.