bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STaphylococcus aureus suRgical Inpatient Vaccine Efficacy (STRIVE) Randomized Clinical Trial
Authors: Hassanzadeh Hamid , Baber James , Begier Elizabeth , Noriega David C , Konishi Hiroaki , Yato Yoshiyuki , Wang Michael Y , Le Huec Jean Charles , Patel Vikas , Varga Peter , Liljenqvist Ulf , Conly John , Sabharwal Charu , Munjal Iona , Cooper David , Radley David , Jaques Anna , Patton Michael , Gruber William C , Jansen Kathrin U , Anderson Annaliesa S , Gurtman Alejandra ,   for the STaphylococcus aureus suRgical Inpatient Vaccine Efficacy Investigator Team, Zenilman Jonathan , Salata Robert , Schaffner William , Blackwelder William , Leaper David
Published: May 2023

Background

Staphylococcus aureus is a global pathogen that is frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S. aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S. aureus infection is critically needed. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation.

Methods

In this multicenter, site-level, randomized, double-blind trial, patients aged 18–85 years received a single dose of SA4Ag or placebo 10–60 days before surgery. SA4Ag efficacy in preventing postoperative S. aureus bloodstream infection and/or deep incisional or organ/space SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed.

Results

Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S. aureus infection (14 cases in each group through postoperative day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups.

Conclusions

In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection.

Clinical Trials Registration. NCT02388165.
Fed Up: The Global Ascension of the Federal Reserve in the Era of Migration
Authors: Connell Brendan J , Shin Adrian J
Published: May 2023

In recent decades, the Federal Reserve has emerged as a global lender of last resort. In this article, we investigate whether the prospect of unwanted migration has driven lawmakers’ support for the Fed's increased international role. During an economic crisis, declines in investor confidence and capital flight to developed economies often cause economic hardship in the developing world, thus encouraging increased migration into advanced industrial economies. Concerned about voter opposition to increased immigration, immigration-averse policymakers of migrant-receiving states will seek ways to reduce the economic distress of migrant-sending states. To corroborate our argument, we analyze congressional voting on the “Audit the Fed” bills in the US House of Representatives from 2012 to 2015. Using the district-level foreign-born population as an indicator of migration pressure, our evidence suggests that anti-immigrant lawmakers are more likely to support the Federal Reserve's international initiatives when their districts face a disproportionately high level of migrant pressure.
From Food Subsidies to Cash Transfers: Assessing Economy-Wide Benefits and Trade-Offs in Egypt
Authors: Breisinger Clemens , Kassim Yumna , Kurdi Sikandra , Randriamamonjy Josee , Thurlow James
Published: May 2023

Food is a vital part of poor households' budgets and so subsidizing staple foods would appear to be an obvious pro-poor policy. Indeed, most countries in North Africa have prioritized large national subsidy programs for staple foods and fuels as their main social safety net. However, these programs account for significant shares of government spending and often drive fiscal deficits, especially when import prices rise. In this paper we use a dynamic Computable General Equilibrium model to evaluate the trade-offs between reducing poverty and managing fiscal balances. The modeling framework allows us to measure the efficiency costs of subsidies compared to cash transfers - switching to the latter is an emerging regional trend. We analyze these issues through a detailed case study of Egypt, where efforts to replace food subsidies with cash transfers is already underway. Data is also available in Egypt to design scenarios that realistically reflect potential targeting effectiveness and administrative costs. We show that replacing broad food subsidies with targeted cash transfers of roughly equivalent fiscal costs can improve the welfare of the poorest households, but the continuation of fiscal deficits results in a deceleration of economic growth. The latter gradually reduces welfare gains for the poor and leads to substantial welfare losses for middle-income households who lose access to subsidies without benefitting from cash transfers. Our findings highlight the political challenges facing subsidy reform programs.
Gareth Matthews on development and deficit
Authors: Bakhurst David
Published: May 2023

This paper argues that Gareth Matthews’ writing on developmental psychology is both a central part of his philosophical legacy and a contribution of enduring interest. Although he engages with figures, such as Piaget and Kohlberg, who are no longer as influential as they once were, his critique of the ‘deficit conception of childhood’ retains its relevance today. While the deficit model holds that any capacity, aptitude, virtue, or skill that a child possesses is a deficient version of the same capacity, aptitude, virtue, or skill, as possessed by adults, Matthews contends that there are some things adults do badly which children do well, and that children's curiosity, wonder, and imaginative insight is something we should respect—indeed envy—and try to learn from. The paper concludes by raising a number of questions and criticisms of Matthews’ approach that his contemporary followers might fruitfully seek to address.
Shaeer’s corporal rotation IV: length-preserving correction of congenital ventral penile curvature
Authors: Shaeer Osama , Shaeer Kamal
Published: May 2023

Background

For cases with severe penile curvature, the loss in length with shortening techniques or the loss in rigidity with incision grafting can compromise the results, hence the advent of Shaeer’s corporal rotation III technique, which corrects the most severe degrees of ventral penile curvature without loss in length, though with a certain degree of narrowing.

Aim

We sought to describe Shaeer’s corporal rotation IV, aiming at correction of moderate-to-severe ventral penile curvature with minimal shortening, minimal narrowing, and minimal mobilization of the neurovascular bundle, among other improvements such as using thicker suture material to decease recurrence while inverting the surgical knots.

Methods

Forty-two patients with congenital ventral penile curvature were selected for the study with a curve ranging from 60° to 90°. Patients were randomized into 1 of the 2 groups: Shaeer’s corporal rotation III (SCR-III) and SCR-IV. In SCR-IV, rotation is used to correct the main brunt of curvature, up to 70% to 80% of the curve. Plication is used to correct the residual curvature up to 100% straightness. This keeps the rotation points fewer and closer to the midline, thereby minimizing narrowing and mobilization of the neurovascular bundle.

Outcomes

Both groups were compared with regard to intraoperative erection angle, length, and girth, before and after rotation, as well as subjectively reported postoperative recurrence, penile sensitivity, satisfaction, and IIEF.

Results

The postcorrection angle was zero for all cases in the 2 groups. Dorsal length decreased by 3% in the SCR-IV group compared with 0.5% in the SCR-III group (2.5% difference). The difference in circumference between the narrowest and widest points was 2% in the SCR-IV group vs 9.3% in the SCR-III group (7.3% difference). The average operative time was 19.2% shorter with SCR-IV. Girth asymmetry was reported in 1 (4.8%) of 21 patients in the SCR-IV group compared with 15 (71.4%) of 21 in the SCR-III group. Partial hyposensitivity of the penis was reported in 9.5% in the SCR-IV group compared with 19% in the SCR-III group.

Clinical Implications

SCR-IV is an improvement over former versions of the technique, with higher patient satisfaction.

Strengths and Limitations

A strength of the study is the long follow-up period. Limitations include being a single-center study and reliance on patient reporting to evaluate recurrence and satisfaction.

Conclusion

The SCR-IV technique corrects moderate and severe degrees of congenital ventral penile curvature, with little or no compromise in penile length, girth, or sensitivity.
A sequent calculus for first-order logic formalized in Isabelle/HOL
Authors: From Asta Halkjær , Schlichtkrull Anders , Villadsen Jørgen
Published: May 2023

We formalize in Isabelle/HOL soundness and completeness of a one-sided sequent calculus for first-order logic. The completeness is shown via a translation from a semantic tableau calculus, whose completeness proof we base on the theory entry ‘First-Order Logic According to Fitting’ by Berghofer in the Archive of Formal Proofs. The calculi and proof techniques are taken from Ben-Ari’s textbook Mathematical Logic for Computer Science (Springer, 2012). We thereby demonstrate that Berghofer’s approach works not only for natural deduction but also constitutes a framework for mechanically checked completeness proofs for a range of proof systems.
Low RNA stability signifies increased post-transcriptional regulation of cell identity genes
Authors: Li Yanqiang , Yi Yang , Lv Jie , Gao Xinlei , Yu Yang , Babu Sahana Suresh , Bruno Ivone , Zhao Dongyu , Xia Bo , Peng Weiqun , Zhu Jun , Chen Hong , Zhang Lili , Cao Qi , Chen Kaifu
Published: May 2023

Cell identity genes are distinct from other genes with respect to the epigenetic mechanisms to activate their transcription, e.g. by super-enhancers and broad H3K4me3 domains. However, it remains unclear whether their post-transcriptional regulation is also unique. We performed a systematic analysis of transcriptome-wide RNA stability in nine cell types and found that unstable transcripts were enriched in cell identity-related pathways while stable transcripts were enriched in housekeeping pathways. Joint analyses of RNA stability and chromatin state revealed significant enrichment of super-enhancers and broad H3K4me3 domains at the gene loci of unstable transcripts. Intriguingly, the RNA m6A methyltransferase, METTL3, preferentially binds to chromatin at super-enhancers, broad H3K4me3 domains and their associated genes. METTL3 binding intensity is positively correlated with RNA m6A methylation and negatively correlated with RNA stability of cell identity genes, probably due to co-transcriptional m6A modifications promoting RNA decay. Nanopore direct RNA-sequencing showed that METTL3 knockdown has a stronger effect on RNA m6A and mRNA stability for cell identity genes. Our data suggest a run-and-brake model, where cell identity genes undergo both frequent transcription and fast RNA decay to achieve precise regulation of RNA expression.
Zinc cluster transcription factors frequently activate target genes using a non-canonical half-site binding mode
Authors: Recio Pamela S , Mitra Nikhil J , Shively Christian A , Song David , Jaramillo Grace , Lewis Kristine Shady , Chen Xuhua , Mitra Robi D
Published: May 2023

Gene expression changes are orchestrated by transcription factors (TFs), which bind to DNA to regulate gene expression. It remains surprisingly difficult to predict basic features of the transcriptional process, including in vivo TF occupancy. Existing thermodynamic models of TF function are often not concordant with experimental measurements, suggesting undiscovered biology. Here, we analyzed one of the most well-studied TFs, the yeast zinc cluster Gal4, constructed a Shea–Ackers thermodynamic model to describe its binding, and compared the results of this model to experimentally measured Gal4p binding in vivo. We found that at many promoters, the model predicted no Gal4p binding, yet substantial binding was observed. These outlier promoters lacked canonical binding motifs, and subsequent investigation revealed Gal4p binds unexpectedly to DNA sequences with high densities of its half site (CGG). We confirmed this novel mode of binding through multiple experimental and computational paradigms; we also found most other zinc cluster TFs we tested frequently utilize this binding mode, at 27% of their targets on average. Together, these results demonstrate a novel mode of binding where zinc clusters, the largest class of TFs in yeast, bind DNA sequences with high densities of half sites.
Characteristics of the Complete Genome of Ageratum Yellow Vein China Virus Infecting Sonchus oleraceus
Authors: Mo Cuiping , Tang Yafei , Chen Jinqing , Cui Lixian , Xie Huiting , Qin Bixia , Cai Jianhe , Li Zhanbiao
Published: May 2023

Sonchus (Sonchus oleraceus) originated from Europe and is now cultivated worldwide. The wild resources of sonchus are very abundant, and it has rich nutritional and medicinal value. In this study, 15 sonchus samples with typical symptoms showing leaf curling, vein thickening, and enations were collected from Guigang and Baise City of Guangxi, China. Diseased sonchus were identified by PCR detection, whole genome sequence amplification, and phylogenetic and recombination analysis. The results showed that all the samples were confirmed infected by begomoviruses, and three full-length viral genomes were obtained from 15 sonchus, named GG7-13, GG8-6, and BS63-5. The full genome lengths were 2,584, 2,735, and 2,746 nt, respectively. The nucleotide identities among the three isolates ranged from 92.67 to 99.93%. All of them shared the highest identities (greater than 91.69%) with other isolates of ageratum yellow vein China virus (AYVCNV) (available on GenBank). According to the guidelines of classification of begomoviruses, the virus isolates obtained in this study are different isolates of AYVCNV; a phylogenetic tree analysis showed that these isolates formed a large branch with three other Guangxi isolates of AYVCNV, indicating their close evolution. The genome structures of GG8-6 and BS63-5 are consistent with the monopartite genome virus of the begomoviruses, and both have six open reading frames (ORFs), while GG7-13 has a 151-nt deletion between C2 and C3, resulting in a mutant strain of only five ORFs. This study is the first report on S. oleraceus infected by ageratum yellow vein China virus.
Experiential Learning of Childhood Growth and Development Through a Pediatric Play Project
Authors: Woodley Lisa K. , Cosgrove Beth , Stone Elizabeth , Stanley Erin , Nance Jennifer , De La Grana Annie
Published: May 2023

The adoption of a new undergraduate nursing curriculum granted the opportunity to develop a new method for teaching growth and development. The Pediatric Play Project was designed as part of clinical experience where students explored principles of growth and development by designing a toy or play activity for a hospitalized pediatric patient. Students exhibited immense creativity while meeting learning outcomes, and the project received positive feedback from students and faculty. With minor refinement of the project, students will continue to gain understanding of the nurse’s role in promoting growth and development for the hospitalized child.
Insights in the Prothrombotic Changes After Implantation of a Left Ventricular Assist Device in Patients with End-Stage Heart Failure: A Longitudinal Observational Study
Authors: Liesdek Omayra C.D. , Urbanus Rolf T. , de Maat Steven , de Heer Linda M. , Ramjankhan Faiz Z. , Sebastian Silvie A.E. , Huisman Albert , de Jonge Nicolaas , Vink Aryan , Fischer Kathelijn , Maas Coen , Suyker Willem J.L. , Schutgens Roger E.G.
Published: May 2023

Thrombus formation is a common complication during left ventricular assist device (LVAD) therapy, despite anticoagulation with vitamin K antagonists (VKA) and a platelet inhibitor. Plasma levels of markers for primary and secondary hemostasis and contact activation were determined before LVAD implantation and 6 and 12 months thereafter in 37 adults with end-stage heart failure. Twelve patients received a HeartMate 3, 7 patients received a HeartWare, and 18 patients received a HeartMate II. At baseline, patients had elevated plasma levels of the platelet protein upon activation, β-thromboglobulin, and active von Willebrand factor in thrombogenic state (VWFa), which remained high after LVAD implantation. Von Willebrand factor levels and VWF activity were elevated at baseline but normalized 12 months after LVAD implantation. High D-dimer plasma levels, at baseline, remained elevated after 12 months. This was associated with an increase in plasma thrombin-antithrombin-complex levels and plasma levels of contact activation marker-cleaved H-kininogen after LVAD implantation. Considering these results it could be concluded that LVAD patients show significant coagulation activation despite antithrombotic therapy, which could explain why patients are at high risk for LVAD-induced thrombosis. Continuous low-grade systemic platelet activation and contact activation may contribute to prothrombotic effects of LVAD.
Intensivist-Led Transportation of Patients on Extracorporeal Membrane Oxygenation: A Single Center Experience
Authors: Liu Nian , Han Xuan , Huang Rui , Yu Chao , Fang Ming , Yang Wei , Zha Yutao , Shao Min
Published: May 2023

This study evaluated the suitability, feasibility, safety, and outcomes of transport of the ECMO-dependent patient (EDP) by EDP transport team (EDPTT) in China. Eighty-two EDPs (forty-one cases on VV ECMO and forty-one cases on VA ECMO) received transport between June 2018 and June 2021 and were retrospectively analyzed. ECMO circulation was performed by the outlying hospital, mainly using percutaneous ECMO cannulation. The EDPTT consists of three intensive therapists, one of whom serves as a team leader, and one intensive care unit nurse. Of these, 81 (98.8%) patients were transferred by ambulance, no deaths occurred during transport, the EDP-related complications were 19% (n = 16); bleeding at the cannula site (n = 7, 8.5%) was the most prominent; equipment-related problems accounted for 14.6% of the problems requiring urgent intervention, with hand cranking being the most common (9.7%). The survival rate during transport was 100%, with 36 (43.9%) patients surviving to discharge. The ECMO weaning rate was 61% for VV ECMO and 63.7% for VA ECMO. The results demonstrated the suitability, feasibility, and safety of transporting EDP in a team led by an intensivist, with few complications and no deaths during transport. This may be the recommended staffing model for EDP transport in developing countries.
Syringomyelia with Charcot arthropathy: A case report
Authors: Yang Tianxiang , Cao Dede , Zhang Bowen , Zhang Jinning , Wang Qiang , Guo Gaopeng , Chen Desheng
Published: May 2023

Background:

Syringomyelia with Charcot arthropathy mainly manifests as skin redness and swelling, local swelling of the joints, paresthesia, joint deformity, and dislocation leading to limited movement, often involving the cervicothoracic spinal cord and shoulder and elbow joints. Furthermore, cases of Charcot arthropathy are rare. In this report, we present the case of a patient with Charcot arthropathy combined with syringomyelia diagnosed at our hospital.

Methods:

The patient was a 42-year-old woman admitted to our hospital with a chief complaint of left elbow swelling lasting for over 20 years, aggravated by limitations of movement for 2 years. The patient completed relevant imaging examination and biopsy for definitive diagnosis.

Results:

Imaging studies led to a suspicion of Charcot arthropathy. Plain radiography and magnetic resonance imaging of the left elbow joint indicated deformity of the joint, with surrounding bone loss and soft tissue swelling. Cervical magnetic resonance imaging indicated syringomyelia between the C5 and T5 levels. The pathological results were consistent with the pathological changes of Charcot arthropathy.

Conclusions:

In clinical work, when a painless joint injury is revealed and the degree of joint disease is extremely disproportionate to the patient’s symptoms, medical workers should consider the possibility of Charcot arthropathy. After carefully performing joint examination, a neurological function examination should be performed as soon as possible, followed by the identification of the cause and intervention, which will improve the quality of life of patients and reduce disability.
Association of systemic lupus erythematosus and acute myeloid leukemia: A case report
Authors: Randrianarisoa Rova Malala Fandresena , Andrianiaina Armel Mamihaja , Sendrasoa Fandresena Arilala , Ramily Samson Léophonte , Razafimaharo Tsiory Iarintsoa , Ratovonjanahary Volatantely , Ramarozatovo Lala Soavina , Rabenja Rapelanoro Fahafahantsoa
Published: May 2023

Rationale:

Systemic lupus erythematosus (SLE) represents a risk of malignancy. The mechanism of carcinogenesis is not fully elucidated. Lymphomas are the most reported cancers in lupus. Other hemopathies have been reported, such as leukemia but remain unusual.

Patient concerns:

We report a 30-year-old woman with SLE diagnosed 20 months ago associated with end-stage renal disease and active hepatitis B. She was treated with hydroxychloroquine and azathioprine, followed by methotrexate. During follow-up, she presented persistent anemia, leukopenia and thrombocytopenia.

Diagnoses:

Following these cytopenias, a bone marrow aspiration was performed. Acute myeloid leukemia associated with SLE was diagnosed.

Interventions:

She received transfusion support and corticosteroid therapy. Methotrexate was stopped and hydroxychloroquine was continued. The patient was not eligible for chemotherapy because of her comorbidities.

Outcomes:

Cytopenias were worsening and unfortunately, she died 3 months later

Lessons:

This observation highlights the importance of regular blood count monitoring during SLE. In case of persistent cytopenia, bone marrow aspiration should be performed to look for an associated hematological malignancy.
C-Clamp Technique: A Retrospective Review of a Novel Technique to Prevent Bladder Injury in Retropubic Midurethral Slings
Authors: Jayne Christopher J. , Bach Madeline , Odulate-Williams Adekorewale , Ocon Adriana , Siddiqui Gazala
Published: May 2023

The original technique for mesh midurethral sling, which utilized a retropubic approach for sling placement, also recognized a risk of simultaneous iatrogenic bladder injury. While synthetic mesh midurethral slings have the criterion standard for SUI treatment, there is still no available technique that entirely eliminates the risk of bladder injury at the time of implantation. The retropubic approach holds a 0.7% to 34% rate of bladder injury. Some providers still opt for the transobturator approach because of a perceived decreased risk of intraoperative bladder perforation. This article describes the “C-clamp technique,” a method directly addressing the perceived key causes of bladder injury via the retropubic approach. This study aimed to determine bladder injury rates upon surgical implantation of retropubic synthetic mesh midurethral sling by 1 provider using the C-clamp technique. The article provides step-by-step instructions for this technique, as well as a link to a video (https://links.lww.com/FPMRS/A362). Briefly, the technique involves use of a deflecting catheter guide in steep Trendelenburg, “clamping” the pubis with the operator's nondominant hand to decrease the retropubic distance, and using the nondominant thumb on the inner curve of the trocar to guide the trocar passage toward the nondominant finger tips and suprapubic exit through the skin.

This retrospective review identified 201 bottom-up retropubic synthetic mesh midurethral slings placed using the C-clamp technique between April 2012 and June 2022. General data collected included average age (51 years), average weight (46–139 kg), average body mass index (BMI, 15–57 kg/m2), and a range of prior surgical procedures and concomitant procedures. Approximately 15% of patients had a history of prior retropubic urethropexy or some form of midurethral sling. There were no lower urinary tract injuries in the entire cohort.

Strengths of this study include its description of the C-clamp technique, the extremes and range of data points included within the study, and the 10-year range of the study. Limitations include its retrospective nature, the single surgeon provider, the vast majority of slings used produced by 1 manufacturer, and limited comprehensive data collection.

Using data from 201 consecutive bottom-up synthetic mesh midurethral sling outcomes during a 10-year span, the authors argue that this technique addresses key anatomic issues contributing to bladder and urethral injury during placement of such slings, with a promising ability to eliminate bladder and urethral injury. Favorable data in a larger number of patients and by multiple providers could provide further support to this technique and support retropubic sling as a preferred method of midurethral sling.
Effect of Correcting Peripheral Refractive Errors on Retinal Sensitivity in Younger and Older Healthy Adults
Authors: João Catarina A. R. , Scanferla Lorenzo , Alarcon Aixa , van der Mooren Marrie , Jansonius Nomdo M.
Published: May 2023

SIGNIFICANCE

Retinal sensitivity decreases with age and age-related eye diseases. Peripheral retinal sensitivity may also be compromised if the refractive correction is not optimized for peripheral vision.

PURPOSE

This study aimed to determine the impact of using a peripheral refractive correction on perimetric thresholds and the influence of age and spherical equivalent on this impact.

METHODS

We measured, in 10 younger (20 to 30 years) and 10 older (58 to 72 years) healthy subjects, perimetric thresholds for Goldmann size III stimulus in several test locations along the horizontal meridian of the visual field (eccentricity, 0, ±10, and ±25°), with default central refractive correction and with peripheral refractive corrections as measured with a Hartmann-Shack wavefront sensor. We used analysis of variance to determine the effect of age and spherical equivalent (between-subject variables) and eccentricity and correction method (central vs. eccentricity specific; within-subject variables) on retinal sensitivity.

RESULTS

Retinal sensitivity was higher if the eyes were optimally corrected for the concerning test location (P = .008), and the effect of this peripheral correction differed between the younger and older subjects (interaction term between group and correction method: P = .02), primarily because of more myopia in the younger group (P = .003). The average improvement by applying peripheral corrections was 1.4 dB in the older subjects and 0.3 dB in the younger subjects.

CONCLUSIONS

Peripheral optical correction has a variable impact on retinal sensitivity, and therefore, assessment of retinal sensitivity may be more accurate if peripheral defocus and astigmatism are corrected.
Refusals of the Determination of Death by Neurologic Criteria: A Mixed Methods Study of Physician Perspectives on Refusals Cases*
Authors: Paquette Erin D. , Ross Lainie F. , Chavez Jairo , Frader Joel E.
Published: May 2023

OBJECTIVES:

Refusals to allow examination for determination of death by neurologic criteria (DNC) challenge pediatric physicians and create distress for medical teams and families of patients suspected to meet criteria for DNC. The objective of this study was to inquire about and assess experiences with such refusals from the perspective of physicians.

DESIGN:

We conducted a mixed-methods survey and interview-based study to understand physicians’ experiences with refusals.

SETTING:

An online survey was sent to pediatric intensivists and neurologists; phone interviews were conducted in a subset.

PATIENTS/PARTICIPANTS:

The study included 80 physician survey respondents and 12 interview physician respondents.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Refusals occur for many reasons regarding patients with both acute and progressive brain injury. The most common reasons were consistent in surveys and interviews and include “waiting on a miracle,” not wanting to give up, religious objections and disbelief in brain death. Time was an important mediator in many cases. Physicians described several approaches to managing refusals, highlighting the impact on medical teams, distraction from other patients, and need for resources to support physicians.

CONCLUSIONS:

Refusals may have important sociodemographic associations that should be considered in managing complex cases. Physicians seek more guidance in law and policies to manage refusals.
The Effects of Expectation Setting and Bundle Consent on Acute Caregiver Stress in the PICU: A Randomized Controlled Trial
Authors: Goldstein Gregory , Karam Oliver , Miller Ferguson Nikki
Published: May 2023

OBJECTIVES:

Having a child admitted to the PICU is a stressful experience for parents and can have long-term negative mental health consequences. The objective was to determine if formalized expectation setting and bundled consent for invasive procedures upon admission impacts the acute stress burden on parents.

DESIGN:

Prospective cluster randomized controlled trial.

SETTING:

Single-center, tertiary PICU.

SUBJECTS:

Parents/guardians of patients, 0–18 years old, admitted to PICU.

INTERVENTIONS:

During experimental weeks, all patients admitted to PICU were bundled-consented for common procedures and given a novel unit introductory letter and “Common Procedures Explained” document. During control weeks, all patients were consented for invasive procedures with separate consents for each procedure. Parents then completed a demographic survey and Stress Overload Scale-Short (SOS-S) 48–72 hours after their child’s admission. For each participant, the SOS-S generates a Personal Vulnerability (PV) score and an Event Load (EL) score. Parents’ perception of the life-threatening nature of their child’s condition was also evaluated.

MEASUREMENTS AND MAIN RESULTS:

Over 73 weeks, 1,882 patients were screened and 261 consented to the SOS-S. Median PV score was 10.4 in the control group and 9.1 in the experimental group (p= 0.15). Median EL score was 11.3 for the control group and 10.5 in the experimental group (p= 0.42). Adjusting for demographic variables and severity of illness, there was no independent association between either PV or EL and bundled consent. However, a parent’s perception of threat-to-life was significantly related to the allocated group (p= 0.036), which resulted in a decreased percentage of parents who rated their child’s illness as “Extremely” life-threatening (experimental group, 17% vs control group, 26%).

CONCLUSIONS:

This study did not demonstrate a decrease in stress when bundled consent was obtained. However, this intervention decreased the parents’ perceived severity of illness. Further multicenter studies are needed to evaluate the effects of bundled consent on parents.
The Future Arrived
Authors: Alkadhi Hatem , Runge Val
Published: May 2023

In the past decades, we have witnessed tremendous technical innovations in computed tomography (CT) imaging. These included improvements in temporal and spatial resolution, lowering of the radiation dose, the introduction of dual-energy and multi-energy imaging, automated image preprocessing and machine learning algorithms, and, most recently, the development and clinical introduction of photon-counting detector CT. This special issue of Investigative Radiology comprises a collection of expert summaries and reviews on this most impactful recent innovation and cutting-edge technology of photon-counting detector CT. It includes articles on technical details about this new CT scanner type and summaries of the first clinical experience in cardiac and vascular imaging, neuroimaging, as well as chest and abdominal imaging, and concludes with an outlook to new contrast agents with potential for k-edge imaging, which are on the horizon.
Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial
Authors: Gruen Danielle S. , Brown Joshua B. , Guyette Francis X. , Johansson Pär I. , Stensballe Jakob , Li Shimena R. , Leeper Christine M. , Eastridge Brian J. , Nirula Raminder , Vercruysse Gary A. , O’Keeffe Terence , Joseph Bellal , Neal Matthew D. , Sperry Jason L.
Published: May 2023

BACKGROUND

In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial.

METHODS

We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors.

RESULTS

We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days (p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors (p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors (p = 0.03).

CONCLUSION

Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Financial toxicity after trauma and acute care surgery: From understanding to action
Authors: Scott John W. , Knowlton Lisa Marie , Murphy Patrick , Neiman Pooja U. , Martin R. Shayn , Staudenmayer Kristan ,   on behalf of the AAST Health Economics Committee
Published: May 2023

Gains in inpatient survival over the last five decades have shifted the burden of major injuries and surgical emergencies from the acute phase to their long-term sequelae. More attention has been placed on evaluation and optimization of long-term physical and mental health; however, the impact of major injuries and surgical emergencies on long-term financial well-being remains a critical blind spot for clinicians and researchers. The concept of financial toxicity encompasses both the objective financial consequences of illness and medical care as well as patients' subjective financial concerns. In this review, representatives of the Healthcare Economics Committee from the American Association for the Surgery of Trauma (1) provide a conceptual overview of financial toxicity after trauma or emergency surgery, (2) outline what is known regarding long-term economic outcomes among trauma and emergency surgery patients, (3) explore the bidirectional relationship between financial toxicity and long-term physical and mental health outcomes, (4) highlight policies and programs that may mitigate financial toxicity, and (5) identify the current knowledge gaps and critical next steps for clinicians and researchers engaged in this work.
Catastrophic health expenditure in nonneurological injury due to motor vehicle crash
Authors: Nishtala Madhuri V. , Reed Madeline , Schumacher Jessica , Hanlon Bret , Venkatesh Manasa , Collins Michael , Zarzaur Ben L.
Published: May 2023

BACKGROUND

Motor vehicle crashes (MVCs) are a leading cause of nonfatal injury in the United States and impose a high financial cost to the patient and the economy. For many patients, this cost may be financially devastating and contribute to worsening health outcomes after injury. We aimed to describe the population level risk of catastrophic health expenditure (CHE) and determine factors associated with risk of CHE.

METHODS

We performed a retrospective review using the 2014–2017 Nationwide Inpatient Sample. The study population consisted of uninsured and privately insured adults aged 26 to 64 years who were hospitalized for nonneurologic traumatic injury due to MVCs. Our measure of financial hardship was CHE, which was defined as hospital charges ≥40% of postsubsistence income. Income estimates were derived from zip-code level data using Γ distribution modeling.

RESULTS

Our sample included 189,000 patients, of which 149,705 had private insurance and 39,375 were uninsured. The median estimated income for the study cohort was $66,118 (interquartile range, $65,353–$66,884). The median cost of hospitalization was $53,467 (interquartile range, $29,854–$99,914). In addition, 91.5% of uninsured patients suffering from MVC are at risk for CHE, and 10.1% of privately insured patients are at risk for CHE. Among the insured, Black, Hispanic, and low income were associated with CHE.

CONCLUSION

Nine of 10 uninsured patients are at risk for CHE after hospitalization for MVC. Despite having insurance, 10% of patients are still at risk of CHE. Black, Hispanic, and low-income communities are at highest risk of having private insurance and still experiencing CHE. This is the first population level analysis after the implementation of the Affordable Care Act that assesses the financial burden of no insurance and underinsurance. These data are important to understand the effectiveness of insurance coverage and guide hospital and policy level interventions to prevent CHE.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
The American Association for the Surgery of Trauma–European Society of Trauma and Emergency Surgery Emergency Surgery Course: Initial experience in Japan
Authors: Morishita Koji , Coimbra Raul , Ito Kaori , Otomo Yasuhiro
Published: May 2023

BACKGROUND

Acute care surgery has recently been recognized as a field of surgery in Japan, but no well-organized nontrauma emergency surgery education system exists. The American Association for the Surgery of Trauma–European Society of Trauma and Emergency Surgery Emergency Surgery Course (AAST-ESTES ESC) course gives surgeons the knowledge and skills to make daily decisions about nontrauma emergency surgery. We held an AAST-ESTES ESC course in Japan from October 2 to 3, 2022.

METHODS

Thirty-two Japanese participants were asked to rate the following items using a 5-point Likert scale from 1 to 5: overall assessment, program subjects, content, instructional style, and activity. In addition, we also inquired about topics that participants intended to change as a result of what they had learned in the course.

RESULTS

All items were rated highly (4.1–4.7) by the participants. Participants reported intending to implement changes concerning mesenteric ischemia, colorectal crises, and acute pancreatitis after taking the course.

CONCLUSION

Japanese surgeons gave the AAST-ESTES ESC course excellent ratings, suggesting its crucial role in Japan, where there has been no development of nontrauma emergency surgery education courses.
Prehospital and emergency department pediatric readiness for injured children: A statement from the American College of Surgeons Committee on Trauma Emergency Medical Services Committee
Authors: Ross Samuel Wade , Campion Eric , Jensen Aaron R. , Gray Lisa , Gross Toni , Namias Nicholas , Goodloe Jeffrey M. , Bulger Eileen M. , Fischer Peter E. , Fallat Mary E.
Published: May 2023

Injury is the leading cause of death in children older than 1 year, and children make up 22% of the population. Pediatric readiness (PR) of the nation's emergency departments and state trauma and emergency medical services (EMS) systems is conceptually important and vital to mitigate mortality and morbidity in this population. The extension of PR to the trauma community has become a focused area for training, staffing, education, and equipment at all levels of trauma center designation, and there is evidence that a higher level of emergency department PR is independently associated with long-term survival among injured children. Although less well studied, there is an associated need for EMS PR, which is relevant to the injured child who needs assessment, treatment, triage, and transport to a trauma center. We outline a blueprint along with recommendations for incorporating PR into trauma system development in this opinion from the EMS Committee of the American College of Surgeons Committee on Trauma. These recommendations are particularly pertinent in the rural and underserved areas of the United States but are directed toward all levels of professionals who care for an injured child along the trauma continuum of care.
Silvio Weidmann: laying the foundations for unravelling the mechanism of heart rhythm
Authors: DiFrancesco Dario , Noble Denis
Published: May 2023

Silvio Weidmann laid the basis of cardiac electrophysiology and was the forerunner in the search for mechanisms governing the electrical activity of the heart in his legendary first studies of Purkinje fibres in the 1950s. His work was the cornerstone of research in this field for many generations, and countless cardiologists and electrophysiologists have based their studies on the knowledge generated by Weidmann's pioneering data. This review summarizes his key contributions from the first intracellular recordings of cardiac membrane potentials in 1949 to the publication of his monograph in 1956. That summary is followed by an imagined dialogue between the authors and Silvio Weidmann himself, in the format of a one-act play. Both of us have such good recollections of our real-life conversations with Silvio Weidmann that we decided we could achieve a better feel for the history and issues by using a dialogue format. We hope that, in that way, we may transmit the character of Silvio Weidmann better for those readers who will not have known him personally. Silvio Weidmann was an extraordinarily sensitive and conversational person as well as a great scientist, and we feel it is worth the effort to convey that fact here.

This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
Feedback contributions to excitation–contraction coupling in native functioning striated muscle
Authors: Salvage Samantha C. , Dulhunty Angela F. , Jeevaratnam Kamalan , Jackson Antony P. , Huang Christopher L.-H.
Published: May 2023

Skeletal and cardiac muscle excitation–contraction coupling commences with Na
v
1.4/Na
v
1.5-mediated, surface and transverse (T-) tubular, action potential generation. This initiates
feedforward
, allosteric or Ca
2+
-mediated, T-sarcoplasmic reticular (SR) junctional, voltage sensor-Cav1.1/Cav1.2 and ryanodine receptor-RyR1/RyR2 interaction. We review recent structural, physiological and translational studies on possible
feedback
actions of the resulting SR Ca
2+
release on Na
v
1.4/Na
v
1.5 function in native muscle. Finite-element modelling predicted potentially regulatory T-SR junctional [Ca
2+
]
TSR
domains. Na
v
1.4/Na
v
1.5, III-IV linker and C-terminal domain structures included Ca
2+
and/or calmodulin-binding sites whose mutations corresponded to specific clinical conditions. Loose-patch-clamped native murine skeletal muscle fibres and cardiomyocytes showed reduced Na
+
currents (
I
Na
) following SR Ca
2+
release induced by the Epac and direct RyR1/RyR2 activators, 8-(4-chlorophenylthio)adenosine-3′,5′-cyclic monophosphate and caffeine, abrogated by the RyR inhibitor dantrolene. Conversely, dantrolene and the Ca
2+
-ATPase inhibitor cyclopiazonic acid increased
I
Na
. Experimental, catecholaminergic polymorphic ventricular tachycardic
RyR2-P2328S
and metabolically deficient
Pgc1β
−/−
cardiomyocytes also showed reduced
I
Na
accompanying [Ca
2+
]
i
abnormalities rescued by dantrolene- and flecainide-mediated RyR block. Finally, hydroxychloroquine challenge implicated action potential (AP) prolongation in slowing AP conduction through modifying Ca
2+
transients. The corresponding tissue/organ preparations each showed pro-arrhythmic, slowed AP upstrokes and conduction velocities. We finally extend discussion of possible Ca
2+
-mediated effects to further, Ca
2+
, K
+
and Cl
−
, channel types.

This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.
FKBP12 binds to the cardiac ryanodine receptor with negative cooperativity: implications for heart muscle physiology in health and disease
Authors: Richardson S. J. , Thekkedam C. G. , Casarotto M. G. , Beard N. A. , Dulhunty A. F.
Published: May 2023

Cardiac ryanodine receptors (RyR2) release the Ca2+from intracellular stores that is essential for cardiac myocyte contraction. The ion channel opening is tightly regulated by intracellular factors, including the FK506 binding proteins, FKBP12 and FKBP12.6. The impact of these proteins on RyR2 activity and cardiac contraction is debated, with often apparently contradictory experimental results, particularly for FKBP12. The isoform that regulates RyR2 has generally been considered to be FKBP12.6, despite the fact that FKBP12 is the major isoform associated with RyR2 in some species and is bound in similar proportions to FKBP12.6 in others, including sheep and humans. Here, we show time- and concentration-dependent effects of adding FKBP12 to RyR2 channels that were partly depleted of FKBP12/12.6 during isolation. The added FKBP12 displaced most remaining endogenous FKBP12/12.6. The results suggest that FKBP12 activates RyR2 with high affinity and inhibits RyR2 with lower affinity, consistent with a model of negative cooperativity in FKBP12 binding to each of the four subunits in the RyR tetramer. The easy dissociation of some FKBP12/12.6 could dynamically alter RyR2 activity in response to changes inin vivoregulatory factors, indicating a significant role for FKBP12/12.6 in Ca2+signalling and cardiac function in healthy and diseased hearts.

This article is part of the theme issue ‘The heartbeat: its molecular basis and physiological mechanisms’.