Propagation of distinct CWD prion strains during peripheral and intracerebral challenges of gene-targeted mice.

Since prion diseases result from infection and neurodegeneration of the central nervous system (CNS), experimental characterizations of prion strain properties customarily rely on the outcomes of intracerebral challenges. However, natural transmission of certain prions, including those causing chronic wasting disease (CWD) in elk and deer, depends on propagation in peripheral host compartments prior to CNS infection. Using gene-targeted GtE and GtQ mice, which accurately control cellular elk or deer PrP expression, we assessed the impact that peripheral or intracerebral exposures play on CWD prion strain propagation and resulting CNS abnormalities. Whereas oral and intraperitoneal transmissions produced identical neuropathological outcomes in GtE and GtQ mice and preserved the naturally convergent conformations of elk and deer CWD prions, intracerebral transmissions generated CNS prion strains with divergent biochemical properties in GtE and GtQ mice that were changed compared to their native counterparts. While CWD replication kinetics remained constant during iterative peripheral transmissions and brain titers reflected those found in native hosts, serial intracerebral transmissions produced 10-fold higher prion titers and accelerated incubation times. Our demonstration that peripherally and intracerebrally challenged Gt mice develop dissimilar CNS diseases which result from the propagation of distinct CWD prion strains points to the involvement of tissue-specific cofactors during strain selection in different host compartments. Since peripheral transmissions preserved the natural features of elk and deer prions, whereas intracerebral propagation produced divergent strains, our findings illustrate the importance of experimental characterizations using hosts that not only abrogate species barriers but also accurately recapitulate natural transmission routes of native strains.

The Rise of Patients Declining Rectal Cancer Surgery in the Era of Total Neoadjuvant Therapy.

BACKGROUND: The treatment landscape for rectal cancer is rapidly evolving, particularly with the increasing use of neoadjuvant therapies. Still, up to 50% of patients with stage II-III disease require surgical resection post-neoadjuvant therapy to achieve the best oncologic outcomes. Many patients, however, hope to avoid surgery. This study aimed to assess trends and factors associated with declining recommended oncologic resection after systemic therapy nationally and in our institution. PATIENTS AND METHODS: This is a retrospective analysis using the National Cancer Database from 2009 to 2021 and an institutional cohort at an academic center between 2009 and 2022 including adults with stage I-III rectal adenocarcinoma who underwent neoadjuvant therapy and were suitable for surgery. RESULTS: Of 96,997 patients nationally, the rate of declining surgery increased from 2.3% in 2009 to 6.3% in 2021, a trend mirrored in our institutional cohort of 365 patients (0% in 2009/2010 to approximately 6-12% in 2021/2022). Locally, patients who declined surgery had higher rates of tobacco use, temporary loss to follow-up during therapy, and a more robust, albeit incomplete, tumor response to neoadjuvant therapy compared with controls who underwent surgery. Despite a stoma being the most cited reason for declining surgery, 30.4% of patients who declined oncologic resection died with a stoma. CONCLUSIONS: Our findings underscore a notable trend of patients declining oncologic resections following neoadjuvant therapy for rectal cancer. By shedding light on the outcomes of patients who opt against surgery, we address a critical gap in the literature essential for informing patients about potential risks.

Association of freeze-dried plasma with 24-h mortality among trauma patients at risk for hemorrhage.

BACKGROUND: Blood products form the cornerstone of contemporary hemorrhage control but are limited resources. Freeze-dried plasma (FDP), which contains coagulation factors, is a promising adjunct in hemostatic resuscitation. We explore the association between FDP alone or in combination with other blood products on 24-h mortality. STUDY DESIGN AND METHODS: This is a secondary data analysis from a cross-sectional prospective observational multicenter study of adult trauma patients in the Western Cape of South Africa. We compare mortality among trauma patients at risk of hemorrhage in three treatment groups: Blood Products only, FDP + Blood Products, and FDP only. We apply inverse probability of treatment weighting and fit a multivariable Cox proportional hazards model to assess the hazard of 24-h mortality. RESULTS: Four hundred and forty-eight patients were included, and 55 (12.2%) died within 24 h of hospital arrival. Compared to the Blood Products only group, we found no difference in 24-h mortality for the FDP + Blood Product group (p = .40) and a lower hazard of death for the FDP only group (hazard = 0.38; 95% CI, 0.15-1.00; p = .05). However, sensitivity analyses showed no difference in 24-h mortality across treatments in subgroups with moderate and severe shock, early blood product administration, and accounting for immortal time bias. CONCLUSION: We found insufficient evidence to conclude there is a difference in relative 24-h mortality among trauma patients at risk for hemorrhage who received FDP alone, blood products alone, or blood products with FDP. There may be an adjunctive role for FDP in hemorrhagic shock resuscitation in settings with significantly restricted access to blood products.

Management of Persistent Low-Suspicion Cervical Lymphadenopathy in Pediatric Patients.

INTRODUCTION: Cervical lymphadenopathy in children is typically self-limited; however, the management of persistent lymphadenopathy remains unclear. This study aimed to evaluate the management and outcomes of patients with persistent cervical lymphadenopathy. METHODS: Single-institution, retrospective review of children <18 years undergoing ultrasound (US) for cervical lymphadenopathy from 2013 to 2021 was performed. Patients were stratified into initial biopsy, delayed biopsy, or no biopsy groups. Clinical characteristics and workup were compared, and multivariate analyses were performed to assess predictors of delayed biopsy. RESULTS: 568 patients were identified, with 493 patients having no biopsy, 41 patients undergoing initial biopsy, and 34 patients undergoing delayed biopsy. Presenting symptoms differed: no biopsy patients were younger, were more likely to present to the emergency department, and had clinical findings often associated with acute illness. Patients with USs revealing abnormal vascularity or atypical architecture were more likely to be biopsied. History of malignancy, symptoms >1 week but <3 months, and atypical or change in architecture on US was associated with delayed biopsy. Patients with long-term follow-up (LTF) were followed for a median of 99.0 days. Malignancies were identified in 12 patients (2.1%). All malignancies were diagnosed within 14 days of presentation, and no malignancies were identified in LTF. CONCLUSIONS: Patients with persistent low suspicion lymphadenopathy are often followed for long durations; however, in this cohort, no malignancies were diagnosed during LTF. We propose an algorithm of forgoing a biopsy and employing primary care surveillance and education, which may be appropriate for these patients in the proper setting.

Estimating cutoff values for diagnostic tests to achieve target specificity using extreme value theory.

BACKGROUND: Rapidly developing tests for emerging diseases is critical for early disease monitoring. In the early stages of an epidemic, when low prevalences are expected, high specificity tests are desired to avoid numerous false positives. Selecting a cutoff to classify positive and negative test results that has the desired operating characteristics, such as specificity, is challenging for new tests because of limited validation data with known disease status. While there is ample statistical literature on estimating quantiles of a distribution, there is limited evidence on estimating extreme quantiles from limited validation data and the resulting test characteristics in the disease testing context. METHODS: We propose using extreme value theory to select a cutoff with predetermined specificity by fitting a Pareto distribution to the upper tail of the negative controls. We compared this method to five previously proposed cutoff selection methods in a data analysis and simulation study. We analyzed COVID-19 enzyme linked immunosorbent assay antibody test results from long-term care facilities and skilled nursing staff in Colorado between May and December of 2020. RESULTS: We found the extreme value approach had minimal bias when targeting a specificity of 0.995. Using the empirical quantile of the negative controls performed well when targeting a specificity of 0.95. The higher target specificity is preferred for overall test accuracy when prevalence is low, whereas the lower target specificity is preferred when prevalence is higher and resulted in less variable prevalence estimation. DISCUSSION: While commonly used, the normal based methods showed considerable bias compared to the empirical and extreme value theory-based methods. CONCLUSIONS: When determining disease testing cutoffs from small training data samples, we recommend using the extreme value based-methods when targeting a high specificity and the empirical quantile when targeting a lower specificity.

A clinician's guide to pulmonary hypertension.

ABSTRACT: Despite advances in diagnosis and treatment, pulmonary hypertension has high morbidity and mortality. The presenting symptoms often are vague and may mimic other more common diseases, so patients can be misdiagnosed or missed early in the disease process. Early detection of pulmonary hypertension by primary care providers can play an important role in patient outcomes and survival. Identifying signs and symptoms, understanding the causes and classifications, and knowing the systematic approach to evaluating and diagnosing patients with suspected pulmonary hypertension are key to preventing premature patient decline.

Novel Prion Strain as Cause of Chronic Wasting Disease in a Moose, Finland.

Our previous studies using gene-targeted mouse models of chronic wasting disease (CWD) demonstrated that Norway and North America cervids are infected with distinct prion strains that respond differently to naturally occurring amino acid variation at residue 226 of the prion protein. Here we performed transmissions in gene-targeted mice to investigate the properties of prions causing newly emergent CWD in moose in Finland. Although CWD prions from Finland and Norway moose had comparable responses to primary structural differences at residue 226, other distinctive criteria, including transmission kinetics, patterns of neuronal degeneration, and conformational features of prions generated in the brains of diseased mice, demonstrated that the strain properties of Finland moose CWD prions are different from those previously characterized in Norway CWD. Our findings add to a growing body of evidence for a diverse portfolio of emergent strains in Nordic countries that are etiologically distinct from the comparatively consistent strain profile of North America CWD.

Implementing an electronic sideband offset lock for isotope shift spectroscopy in radium.

We demonstrate laser frequency stabilization with at least 6 GHz of offset tunability using an in-phase/quadrature (IQ) modulator to generate electronic sidebands (ESB) on a titanium sapphire laser at 714 nm and we apply this technique to perform isotope shift spectroscopy of 226Ra and 225Ra. By locking the laser to a single resonance of a high finesse optical cavity and adjusting the lock offset, we determine the frequency difference between the magneto-optical trap (MOT) transitions in the two isotopes to be 2630.0 ± 0.3 MHz, a factor of 29 more precise than the previously available data. Using the known value of the hyperfine splitting of the 3P1 level, we calculate the isotope shift for the 1S0 to 3P1 transition to be 2267.0 ± 2.2 MHz, a factor of 8 more precise than the best available value. Our technique could be applied to countless other atomic systems to provide unprecedented precision in isotope shift spectroscopy and other relative frequency comparisons.

The Impact of Nurse Practitioner Care and Accountable Care Organization Assignment on Skilled Nursing Services and Hospital Readmissions.

BACKGROUND: Accountable care organizations (ACOs) and the employment of nurse practitioners (NP) in place of physicians are strategies that aim to reduce the cost and improve the quality of routine care delivered in skilled nursing facilities (SNF). The recent expansion of ACOs and nurse practitioners into SNF settings in the United States may be associated with improved health outcomes for patients. OBJECTIVES: To determine the relationship between ACO attribution and NP care delivery during SNF visits and the relationship between NP care delivery during SNF visits and unplanned hospital readmissions. METHODS: We obtained a sample of 527,329 fee-for-service Medicare beneficiaries with 1 or more SNF stays between 2012 and 2017. We used logistic regression to measure the association between patient ACO attribution and evaluation and management care delivered by NPs in addition to the relationship between evaluation and management services delivered by NPs and hospital readmissions. RESULTS: ACO beneficiaries were 1.26% points more likely to receive 1 or more E&M services delivered by an NP during their SNF visits [Marginal Effect (ME): 0.0126; 95% CI: (0.009, 0.0160)]. ACO-attributed beneficiaries receiving most of their E&M services from NPs during their SNF visits were at a lower risk of readmission than ACO-attributed beneficiaries receiving no NP E&M care (5.9% vs. 7.1%; P <0.001). CONCLUSIONS: Greater participation by the NPs in care delivery in SNFs was associated with a reduced risk of patient readmission to hospitals. ACOs attributed beneficiaries were more likely to obtain the benefits of greater nurse practitioner involvement in their care.

Patient Cognitive Status and Physician Recommendations for Cardiovascular Disease Treatment: Results of Two Nationwide, Randomized Survey Studies.

BACKGROUND: Clinical guidelines recommend that older patients (65+) with mild cognitive impairment (MCI) and early-stage dementia receive similar guideline-concordant care after cardiovascular disease (CVD) events as those with normal cognition (NC). However, older patients with MCI and dementia receive less care for CVD and other conditions than those with NC. Whether physician recommendations for guideline-concordant treatments after two common CVD events, acute myocardial infarction (AMI) and acute ischemic stroke (stroke), differ between older patients with NC, MCI, and early-stage dementia is unknown. OBJECTIVE: To test the influence of patient cognitive status (NC, MCI, early-stage dementia) on physicians' recommendations for guideline-concordant treatments for AMI and stroke. DESIGN: We conducted two parallel, randomized survey studies for AMI and stroke in the US using clinical vignettes where the hypothetical patient's cognitive status was randomized between physicians. PARTICIPANTS: The study included cardiologists, neurologists, and generalists who care for most patients hospitalized for AMI and stroke. MAIN MEASURES: The primary outcome was a composite quality score representing the number of five guideline-concordant treatments physicians recommended for a hypothetical patient after AMI or stroke. KEY RESULTS: 1,031 physicians completed the study (58.5% response rate). Of 1,031 respondents, 980 physicians had complete information. After adjusting for physician factors, physicians recommended similar treatments after AMI and stroke in hypothetical patients with pre-existing MCI (adjusted ratio of expected composite quality score, 0.98 [95% CI, 0.94, 1.02]; P = 0.36) as hypothetical patients with NC. Physicians recommended fewer treatments to hypothetical patients with pre-existing early-stage dementia than to hypothetical patients with NC (adjusted ratio of expected composite quality score, 0.90 [0.86, 0.94]; P < 0.001). CONCLUSION: In these randomized survey studies, physicians recommended fewer guideline-concordant AMI and stroke treatments to hypothetical patients with early-stage dementia than those with NC. We did not find evidence that physicians recommend fewer treatments to hypothetical patients with MCI than those with NC.

Recovery of Skill Decay After COVID-19 Redeployments and Implications for Competency Attainment.

INTRODUCTION: The COVID-19 pandemic immediately interrupted procedural training. The lasting impact of reduced caseloads and service redeployments on procedural-resident training has been underexplored. This longitudinal study investigated the long-term perspectives of skill decay after short breaks in training and implications for ensuring resident competency attainment. METHODS: Web-based cross-sectional surveys distributed immediately after (June 2020) compared to 1 y after (July 2021) COVID-19 redeployments at two tertiary academic medical centers of an integrated health system in New York. Participants included general surgery, surgical subspecialty, and anesthesiology residents and faculty. RESULTS: Fifty-five residents and 33 faculty completed the survey. Ninety-point nine percent of residents and 36.4% of faculty were redeployed to COVID-ICUs. Sixty-three-point seven percent of residents and 75.0% of faculty reported a reduction in resident technical skills in the short-term, with significantly less (45.5% of residents and 21.2% of faculty) reporting persistent reduction in technical skill after 1 y (P = 0.001, P < 0.001). Seventy-five percent of residents and 100% of faculty were confident residents would be able to practice independently at the conclusion of their training. Sixty-five-point five percent of residents and 63.6% of faculty felt that residents experienced a durable improvement in critical care skills. Residents also reported a positive long-term impact on professional core competencies at 1 y. CONCLUSIONS: Longitudinal surveillance of residents after COVID-19 redeployments suggests washout of temporary skill decay and return of resident confidence upon resumption of traditional training. This may provide insight into the impact of other short-term training interruptions on resident skill and promote greater resident support upon training resumption to ensure competency attainment.

The value of performing cerebrovascular CT angiography in major trauma patients: a 5-year retrospective review.

AIM: To assess whether routine cerebrovascular imaging is required in all major trauma (MT) patients. MATERIALS AND METHODS: All MT patients with cerebrovascular imaging between January 2015 and December 2020 were included in the study. Data were collated regarding the type of indication for computed tomography (CT) angiography imaging, time interval from the initial trauma, relevant trauma diagnoses on initial trauma imaging, and CT angiography. Findings, such as aneurysms, vascular malformations, luminal thrombus, venous sinus thrombosis, or vascular injury, were collated. Subsequent treatment with anti-coagulants/anti-platelets or surgical/radiological intervention was noted. Follow-up imaging was assessed for residual injury or complications. RESULTS: Two hundred and fifty of the 6,251 MT patients underwent dedicated cerebrovascular imaging and were included in the study. Of these 41 (16.4%) had cervical artery or venous sinus injury. Further positive vascular findings were identified in 25/250 patients who presented with an incidental stroke or a vascular abnormality and were mislabelled as MT patients at presentation. One patient with a carotid injury subsequently died following a large infarction. Another patient with vertebral artery injury suffered a non-lethal stroke. No patients underwent surgery or intervention. CONCLUSION: The present study showed that the overall incidence of detected blunt cerebrovascular injuries was very low (0.6%) and even lower for symptomatic vascular injury (0.03%). Routine cerebrovascular imaging is not recommended in all MT trauma patients, but instead, a continued case-by-case basis should be considered.

Leadership Science in Nursing: Creating New Solutions for New Challenges.

The Association for Leadership Science in Nursing (ALSN) November 2022 International Conference was held at the Frances Payne Bolton School of Nursing at Case Western University. ALSN is dedicated to uniting academic and practice leaders to shape leadership science, education in nursing, and the practice of nursing leadership. One hundred fifty-one nurse leaders from the United States, Canada, and Oman gathered to discuss leadership as highlighted in this column.

Influence of mild cognitive impairment on patient and care partner decision-making for acute ischemic stroke.

GOALS: Evidence suggests that patients with mild cognitive impairment (MCI) receive fewer treatments for acute ischemic stroke and other cardiovascular diseases than patients with normal cognition. Little is known about how patient and care partner preferences for ischemic stroke treatment differ between the patient population with MCI and the population with normal cognition. This study aimed to understand how patient MCI diagnosis influences patient and care partner decision-making for acute ischemic stroke treatments. METHODS: Multi-center qualitative study using in-person semi-structured interviews with 20 MCI and normal cognition patient-care partner dyads using a standard guide. The present study reports results on patient and care partner preferences for a clinical vignette patient to receive three non-invasive treatments (intravenous tissue plasminogen activator, inpatient rehabilitation, and secondary preventive medications) and two invasive treatments (feeding tube and carotid endarterectomy) after acute ischemic stroke. We used qualitative content analysis to identify themes. FINDINGS: We identified three major themes: (1) Patients with MCI desired non-invasive treatments after stroke, similar to patients with normal cognition and for similar reasons; (2) Patients with MCI expressed different preferences than patients with normal cognition for two invasive treatments after stroke: carotid endarterectomy and feeding tube placement; and (3) Patients with MCI expressed more skepticism of the stroke treatment options and less decisiveness in decision-making than patients with normal cognition. CONCLUSIONS: These results suggest that patient MCI diagnosis may contribute to differences in patient and care partner preferences for invasive treatments after stroke, but not for non-invasive treatments.

Exploration of System Chief Nurse Executive's Leadership Practices to Support, Mentor, Develop, and Retain Nurse Leaders.

In 2019, the National Academy of Science identified clinician burnout as a growing public health concern. The COVID-19 pandemic has only compounded this crisis and transformed it into an escalating fracture within the US health care system. Concurrently evolving with this emergency is a rise in the number of nurses who intend to leave the profession. Frontline nurse leaders are the lynchpin in ensuring health care systems function. These leaders have accountability over patient care and clinician well-being. Focused efforts must address clinician burnout. However, without addressing the well-being of frontline nurse leaders, the fault line in our health care system becomes a vast chasm. Recently, published literature began to emerge describing and addressing frontline clinician burnout. Unfortunately, only a few, if any, address issues related to leaders. The aim of this qualitative case study research was to explore and discover general themes in system chief nurse executive leadership practices that support, mentor, develop, and retain nurse leaders as a basis for future research. Three major themes were identified for future study and exploration: enhancing leadership development programs; improving leader work environments; and focusing on leader well-being and support. Further research is needed to evaluate the effectiveness of these themes.

ß-Nuclear-Recoil Correlation from

We report the first precise measurement of a ß-recoil correlation from a radioactive noble gas (^{6}He) confined via a magneto-optical trap. The measurement is motivated by the search for exotic tensor-type contributions to the charged weak current. Interpreted as tensor currents with right-handed neutrinos, the measurements yield |C_{T}/C_{A}|^{2}≤0.022 (90% confidence limit, C.L.). On the other hand, for left-handed neutrinos the limits are 0.007

The Association Between Mild Cognitive Impairment Diagnosis and Patient Treatment Preferences: a Survey of Older Adults.

BACKGROUND: Older patients (65+) with mild cognitive impairment (MCI) receive less guideline-concordant care for cardiovascular disease (CVD) and other conditions than patients with normal cognition (NC). One potential explanation is that patients with MCI want less treatment than patients with NC; however, the treatment preferences of patients with MCI have not been studied. OBJECTIVE: To determine whether patients with MCI have different treatment preferences than patients with NC. DESIGN: Cross-sectional survey conducted at two academic medical centers from February to December 2019 PARTICIPANTS: Dyads of older outpatients with MCI and NC and patient-designated surrogates. MAIN MEASURES: The modified Life-Support Preferences-Predictions Questionnaire score measured patients' preferences for life-sustaining treatment decisions in six health scenarios including stroke and acute myocardial infarction (range, 0-24 treatments rejected with greater scores indicating lower desire for treatment). KEY RESULTS: The survey response rate was 73.4%. Of 136 recruited dyads, 127 (93.4%) completed the survey (66 MCI and 61 NC). The median number of life-sustaining treatments rejected across health scenarios did not differ significantly between patients with MCI and patients with NC (4.5 vs 6.0; P=0.55). Most patients with MCI (80%) and NC (80%) desired life-sustaining treatments in their current health (P=0.99). After adjusting for patient and surrogate factors, the difference in mean counts of rejected treatments between patients with MCI and patients with NC was not statistically significant (adjusted ratio, 1.08, 95% CI, 0.80-1.44; P=0.63). CONCLUSION: We did not find evidence that patients with MCI want less treatment than patients with NC. These findings suggest that other provider and system factors might contribute to patients with MCI getting less guideline-concordant care.

The Healthy Disruption of Anger.

During the COVID-19 pandemic, information related to the virus changed so rapidly, and anxiety among healthcare workforce mounted exponentially. The reality of the situation was fluid; leadership had a challenging time communicating even short-term strategies. What evolved was a scared, tired, angry healthcare workforce. Association for Leadership Science in Nursing authors explore leaderships' opportunity to acknowledge, harness, and transform this anger into healthy disruption.

ALSN 2021 Conference: Nursing Science for Leadership in the New Decade.

The Association for Leadership Science in Nursing's 2021 conference provided an opportunity to further enhance professional understanding of the difficulties facing nurse leaders as the COVID-19 pandemic continues to create unimaginable challenges. Presentations provided evidence in support of courageous caring leadership interventions.

Prenatal Recognition of Hepatopulmonary Fusion in Right-Sided Congenital Diaphragmatic Hernia for Successful Operative Planning.

INTRODUCTION: Hepatopulmonary fusion (HPF) is a rare anomaly specifically associated with right-sided congenital diaphragmatic hernia (CDH). Fewer than 50 cases of HPF have been reported, most at the time of surgery or postmortem with an associated high morbidity and mortality rate. Prenatal diagnosis and optimal management of these rare cases have not been established. CASE PRESENTATION: We present a case of HPF diagnosed prenatally by fetal ultrasound and magnetic resonance imaging allowing postnatal and intraoperative planning leading to successful HPF separation and repair of the CDH. DISCUSSION: The prenatal recognition allowed the use of preoperative computed tomography angiogram and right cardiac catheterization to plan the surgical approach. Intraoperative ultrasound confirmed abnormal vasculature associated with the HPF facilitating a successful complete HPF separation and CDH repair was performed. The patient survived and continues to do well on long-term follow-up. Prenatal recognition may help reduce the high morbidity and mortality associated with HPF.