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ZongYao Wang,1 John S Sundy,1 Catherine M Foss,1 Huiman X Barnhart,2 Scott M Palmer,1 Sallie D Allgood,3 Evan Trudeau,1 Katie M Alexander,3 Marc C Levesque31Division of Pulmonary, Allergy and Critical Care Medicine, 2Duke Clinical Research Institute, 3Division of Rheumatology and Immunology, Duke University Medical Center, Durham, NC, USABackground: The CD14 C-159T single nucleotide polymorphism (SNP) has been investigated widely as a candidate genetic locus in patients with allergic disease. There are conflicting results for the association of the CD14 C-159T SNP with total serum immunoglobulin E (IgE) levels and atopy. There are limited data regarding the association of the CD14 C-159T SNP in subjects of African ancestry. The aim of the study was to determine whether the C-159T SNP and other CD14 SNPs (C1188G, C1341T) were associated with total serum IgE levels and with allergy skin test results in nonatopic and atopic subjects; as well as in Caucasian and African American subjects.Methods: A total of 291 participants, 18–40 years old, were screened to determine whether they were atopic and/or asthmatic. Analyses were performed to determine the association between CD14 C-159T, C1188G, or C1341T genotypes with serum IgE levels and with the number of positive skin tests among Caucasian or African American subjects.Results: We found no significant association of serum total IgE level with CD14 C-159T, C1188G, or C1341T genotypes within nonatopic or atopic subjects. Subjects with CD14-159 T alleles had significantly more positive allergen skin tests than subjects without CD14-159 T alleles (P = 0.0388). There was a significant association between the CD14 1188 G allele, but not the CD14 1341 T allele, with the number of positive skin-test results in Caucasians, but not in African Americans.Conclusion: These results support a possible association between CD14 polymorphisms and atopy. CD14-159 T or CD14 1188 G alleles were associated with atopic disease. For subjects with CD14 1188 G alleles, the association with atopic disease was stronger in Caucasians compared to African Americans.Keywords: total serum immunoglobulin E, IgE, skin prick test, SPT, CD14-159T, single nucleotide polymorphism, SNP, lipopolysaccharide, LPS, endotoxin

A Discrete Global Grid System (DGGS) is a type of spatial reference system that tessellates the globe into many individual, evenly spaced, and well-aligned cells to encode location and, thus, can serve as a basis for data cube construction. This facilitates integration and aggregation of multi-resolution data from various sources to rapidly calculate spatial statistics. We calculated normalized area and compactness for cell geometries from 5 open-source DGGS implementations - Uber H3, Google S2, RiskAware OpenEAGGR, rHEALPix by Landcare Research New Zealand, and DGGRID by Southern Oregon University - to evaluate their suitability for a global-level statistical data cube. We conclude that the rHEALPix and OpenEAGGR and DGGRID ISEA-based DGGS definitions are most suitable for global statistics because they have the strongest guarantee of equal area preservation - where each cell covers almost exactly the same area on the globe. Uber H3 has the smallest shape distortions, but Uber H3 and Google S2 have the largest variations in cell area. However, they provide more mature software library functionalities. DGGRID provides excellent functionality to construct grids with desired geometric properties but as the only implementation does not provide functions for traversal and navigation within a grid after its construction.

Study region:: The Baltic countries (Estonia, Latvia, Lithuania), North Eastern Europe. Study focus:: Time series models are a convenient tool for modeling hydraulic head time series due to their parsimonious parameterization and quick calculation time. However, it is unclear how the model structure and the outcome relate to the respective site characteristics. Time series modeling with impulse response functions was used to model the head time series. The correlations between the model performance and the environmental settings and between the model parameters and the environmental settings were analyzed using Spearman rank correlation and Random Forest regression analyses. New hydrological insights:: From the 460 analyzed head time series, 145 were modeled with satisfactory goodness-of-fit in the calibration period, using only precipitation, potential evaporation, and temperature as model inputs. This number decreased to 68 time series with a satisfactory fit in the validation period. Including additional drivers in wells where a substantial influence is characteristic could improve modeling results. The model results suggest that snow processes are affecting head dynamics in many wells in the Baltic countries. Most correlations between the model performance and the environmental setting were observed with the geological and climatic setting of the site. Models performed best in monitoring wells with shallow groundwater and lower precipitation seasonality.

Study region: The Porijõgi catchment in Estonia, Northern Europe. Study focus: The lack of adequate precipitation gauges has long been a major obstacle for hydrological modeling. To date, the global availability of satellite and reanalysis precipitation (SRP) products at an increasingly high spatiotemporal resolution has made their use in hydrological applications possible. This study focuses on a comprehensive evaluation of the hydrological applicability of five SRP products. The evaluations were carried out in two parts: (1) evaluating the quality of satellite and reanalysis-based precipitation products relative to gauge observations, and (2) comparing gauge-simulated streamflow with SRP-based simulations using the SWAT model. New hydrological insights for the region: Our results show moderate variation in the detection capability of SRP products and in their influence on streamflow simulations. None of the products performed well with daily-scale predictions. The IMERG, ERA5, and PERSIANN-CDR products showed the best detection capability for the monthly precipitation and demonstrated reliable performance to simulate the monthly streamflow (0.65 < Nash–Sutcliffe efficiency coefficient < 0.75). However, the SM2RASC and CMORPH-CRT products tended to underestimate the gauged precipitation and provided unsatisfactory performance in streamflow simulation. Overall, our findings suggest that SRP products can be a priori alternative sources of precipitation data suitable for hydrological applications in poorly gauged areas.

ROTATIONPLASTY is a surgical procedure that may be appropriate for children with severe congenital femoral deficiency or children with malignant tumors of the femur or proximal tibia. OSTEOTOMIES AND RESECTION of the femur and tibia are performed, allowing the patient's foot to be rotated 180 degrees and reattached while preserving the nerves, muscles, and blood supply. THE POSTERIOR-FACING FOOT functions as the patient's knee joint in a specially fitted prosthesis. Although the outcome is visually unusual, for some children, regaining function and physical capabilities outweighs cosmetic concerns. The surgical procedure is technically challenging and requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

Freely available global digital elevation models (DEMs) are important inputs for many research fields and applications. During the last decade, several global DEMs have been released based on satellite data. ASTER and SRTM are the most widely used DEMs, but the more recently released, AW3D30, TanDEM-X and MERIT, are being increasingly used. Many researchers have studied the quality of these DEM products in recent years. However, there has been no comprehensive and systematic evaluation of their quality over areas with variable topography and land cover conditions. To provide this comparison, we examined the accuracy of six freely available global DEMs (ASTER, AW3D30, MERIT, TanDEM-X, SRTM, and NASADEM) in four geographic regions with different topographic and land use conditions. We used local high-precision elevation models (Light Detection and Ranging (LiDAR), Pleiades-1A) as reference models and all global models were resampled to reference model resolution (1m). In total, 608 million 1x1 m pixels were analyzed. To estimate the accuracy, we generated error rasters by subtracting each reference model from the corresponding global DEM and calculated descriptive statistics for this difference (e.g., median, mean, root-mean-square error (RMSE)). We also assessed the vertical accuracy as a function of the slope, slope aspect, and land cover. We found that slope had the strongest effect on DEM accuracy, with no relationship for slope aspect. The AW3D30 was the most robust and had the most stable performance in most of the tests and is therefore the best choice for an analysis of multiple geographic regions. SRTM and NASADEM also performed well where available, whereas NASADEM, as a successor of SRTM, showed only slight improvement in comparison to SRTM. MERIT and TanDEM-X also performed well despite their lower spatial resolution.

We analyzed the corpus of three geoscientific journals to investigate if there are enough locational references in research articles to apply a geographical search method, such as the example of New Zealand. Based on all available abstracts and all freely available papers of the “New Zealand Journal of Geology and Geophysics”, the “New Zealand Journal of Marine and Freshwater Research”, and the “Journal of Hydrology, New Zealand”, we searched title, abstracts, and full texts for place name occurrences that match records from the official Land Information New Zealand (LINZ) gazetteer. We generated ISO standard compliant metadata records for each article including the spatial references and made them available in a public catalogue service. This catalogue can be queried for articles based on authors, titles, keywords, topics, and spatial reference. We visualize the results in a map to show which area the research articles are about, and how much and how densely geographic space is described through these geoscientific research articles by mapping mentioned place names by their geographic locations. We outlined the methodology and technical framework for the geo-referencing of the journal articles and the platform design for this knowledge inventory. The results indicate that the use of well-crafted abstracts for journal articles with carefully chosen place names of relevance for the article provides a guideline for geographically referencing unstructured information like journal articles and reports in order to make such resources discoverable through geographical queries. Lastly, this approach can actively support integrated holistic assessment of water resources and support decision making.

Background: A significant genetic component has been described for idiopathic pulmonary fibrosis (IPF). The R131H (rs1801274) polymorphism of the IgG receptor FcγRIIa determines receptor affinity for IgG subclasses and is associated with several chronic inflammatory diseases. We investigated whether this polymorphism is associated with IPF susceptibility or progression.Methods: In a case-control study, we compared the distribution of FcγRIIa R131H genotypes in 142 patients with IPF and in 218 controls using allele-specific PCR amplification.Results: No differences in the frequency of FcγRIIa genotypes were evident between IPF patients and control subjects. However, significantly impaired pulmonary function at diagnosis was observed in HH compared to RR homozygotes, with evidence of more severe restriction (reduced forced vital capacity (FVC)) and lower diffusing capacity for carbon monoxide (DLCO). Similarly, increased frequency of the H131 allele was observed in patients with severe disease (DLCO < 40% predicted) (0.53 vs. 0.38; p = 0.03). Furthermore, the H131 allele was associated with progressive pulmonary fibrosis as determined by > 10% drop in FVC and/or > 15% fall in DLCO at 12 months after baseline (0.48 vs. 0.33; p = 0.023).Conclusions: These findings support an association between the FcγRIIa R131H polymorphism and IPF severity and progression, supporting the involvement of immunological mechanisms in IPF pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: "Test-enhanced learning" is a strategy utilized to impact knowledge retention. This study aimed to assess the effect of the frequency of spaced retrieval using repeat testing on knowledge depreciation in a Doctor of Pharmacy (PharmD) Program., Methods: The study randomly assigned second-year pharmacy students to one of three retrieval practice groups: (1) two retrieval practice assessments (2 and 4 months after the course), (2) one retrieval practice assessment (4 months after the course), or (3) no retrieval practice. A final assessment was administered to all participants 6 months after the course. The retrieval assessments and final assessment consisted of five multiple-choice questions on asthma pharmacotherapy., Results: In total, 94 participants were included in the study, with 32 in Group 1 and 31 in both Groups 2 and 3. All three groups performed similarly on the final assessment regardless of the frequency of spaced retrieval. While Group 1 scored numerically higher than Group 2 on the 4-month retrieval practice assessment and did not impact performance on the final assessment. In Group 1, final assessment scores were decreased compared to the two previous retrieval assessments., Conclusion: Regardless of the frequency of spaced retrieval following the academic course where asthma pharmacotherapy was initially learned, retrieval practice using multiple choice assessments, with the gap times of this study, did not impact asthma pharmacotherapy knowledge depreciation among second-year student pharmacists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: In the phase 3 randomized controlled study, ATTRibute-CM, acoramidis, a transthyretin (TTR) stabilizer, demonstrated significant efficacy on the primary endpoint. Participants with transthyretin amyloid cardiomyopathy (ATTR-CM) who completed ATTRibute-CM were invited to enroll in an open-label extension study (OLE). We report efficacy and safety data of acoramidis in participants who completed ATTRibute-CM and enrolled in the ongoing OLE., Methods: Participants who previously received acoramidis through Month 30 (M30) in ATTRibute-CM continued to receive it (continuous acoramidis), and those who received placebo through M30 were switched to acoramidis (placebo to acoramidis). Participants who received concomitant tafamidis in ATTRibute-CM were required to discontinue it to be eligible to enroll in the OLE. Clinical efficacy outcomes analyzed through Month 42 (M42) included time to event for all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH), ACM alone, first CVH alone, ACM or recurrent CVH, change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), serum TTR, and the Kansas City Cardiomyopathy Questionnaire Overall Summary score (KCCQ-OS). Safety outcomes were analyzed through M42., Results: Overall, 438 of 632 participants in ATTRibute-CM completed treatment and 389 enrolled in the ongoing OLE (263 continuous acoramidis, 126 placebo to acoramidis). The hazard ratio (HR) (95% CI) for ACM or first CVH was 0.57 (0.46, 0.72) at M42 based on a stratified Cox proportional hazards model ( P -value < 0.0001) favoring continuous acoramidis. Similar analyses were performed on ACM alone and first CVH alone, with HRs (95% CI) of 0.64 (0.47, 0.88) and 0.53 (0.41, 0.69), respectively, at M42. Treatment effects for NT-proBNP and 6MWD also favored continuous acoramidis. Upon initiation of open-label acoramidis in the placebo-to-acoramidis arm there was a prompt increase in serum TTR. Quality of life assessed by KCCQ-OS was well preserved in continuous acoramidis participants compared with the placebo to acoramidis participants. No new clinically important safety issues were identified in this long-term evaluation., Conclusions: Early initiation and continuous use of acoramidis in the ATTRibute-CM study through M42 of the ongoing OLE study was associated with sustained clinical benefits in a contemporary ATTR-CM cohort, with no clinically important safety issues newly identified.

Competing Interests: Disclosures MGK reports institutional research support from Pfizer, BridgeBio Pharma, Alnylam Pharmaceuticals, and Ionis Pharmaceuticals, consulting/advisory board support from BridgeBio Pharma and Alnylam Pharmaceuticals, and is a member of Alnylam Pharmaceuticals Speaker's Bureau. OAO receives research support from National Institute on Minority Health and Health Disparities (5R01-MD016401) KMA has received an investigator-initiated research grant from Alnylam and consulting fees from Arbor Biotechnologies, Attralus, Intellia, and Prothena. SHS reports research funding through sponsored research agreements to Duke University from Astra Zeneca, Lilly, and Verily and is a coinventor of unlicensed patents held by Duke University. SS receives research support from the National Heart, Lung, and Blood Institute (K23HL161348), Doris Duke Charitable Foundation (#2020061), American Heart Association (#935275), the Mandel Foundation, Duke Heart Center Leadership Council, the Institute for Translational Medicine and Therapeutics, and Foundation for Sarcoidosis Research and has participated in advisory boards for AstraZeneca. All other authors report no relevant disclosures.

Background : The optimal ampicillin-sulbactam dosing regimen for carbapenem-susceptible Acinetobacter baumannii isolates in critically ill trauma patients has not been clearly defined. One strategy to provide the adequate sulbactam dose includes high-dose continuous infusion. Case(s) Description: We present three cases of critically ill trauma patients with augmented renal clearance treated with high-dose ampicillin-sulbactam through an intravenous continuous infusion for ventilator-associated pneumonia. All A. baumannii isolates were susceptible to sulbactam with low minimum inhibitory concentrations. All achieved clinical cure at the end of therapy and no recurrent pneumonia was noted. No clinically substantial adverse effect attributable to ampicillin-sulbactam therapy occurred. Discussion: There is limited evidence to endorse high-dose, continuous infusion ampicillin-sulbactam for treatment of infections caused by carbapenem-susceptible A. baumannii . This report presents three critically ill trauma patients with augmented renal clearance that achieved positive clinical outcomes with higher doses of ampicillin-sulbactam administered through a continuous infusion.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A Medical Subject Heading-based, filtered search returned 2336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high-impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Limited real-world evidence exists for outcomes with contemporary guideline-directed medical therapy (GDMT) or GDMT with implantable cardioverter-defibrillator (ICD)/cardiac resynchronization therapy defibrillator (CRT-D) therapy for patients with heart failure with reduced ejection fraction (HFrEF) and left ventricular ejection fraction (LVEF) ≤35%., Objective: The present study aimed to assess survival associated with GDMT or GDMT with ICD/CRT-D therapy., Methods: This retrospective observational study included real-world de-identified data from January 1, 2016, to December 19, 2023, from 24 U.S. institutions per participating institutional agreements (egnite Database; egnite, Inc.). Patients with a diagnosis of HFrEF and an echocardiographic study documenting LVEF ≤35% were included for analysis., Results: Of 43,591 patients with eligible index event of LVEF ≤35%, prescription history through ≥1 year preindex, and no ICD/CRT-D therapy preindex, mean ± standard deviation age at index was 71.2 ± 13.2 years; 14,805 (34.0%) patients were female. At 24 months, an estimated 99.1% (95% confidence interval [CI] 99.0%-99.2%), 89.9% (95% CI 89.7%-90.1%), 54.8% (95% CI 54.4%-55.2%), and 17.2% (95% CI 16.9%-17.5%), had ≥1, 2, 3, or all 4 GDMT classes prescribed, respectively; an estimated 15.7% (95% CI 15.3%-16.1%) had device placement. Of those without a device, by 24 months, an estimated 45.1% (95% CI 44.4%-45.7%) had a documented LVEF >35%. Counts of GDMT classes prescribed as well as ICD/CRT-D device therapy were associated with lower mortality risk in this population, even after adjustment for patient age, sex, and comorbidities., Conclusion: Both GDMT classes prescribed and device therapy were independently associated with lower mortality risk, even in the presence of more GDMT options for this more contemporary population., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Introduction: Studies have demonstrated that trauma patients with early-ventilator associated pneumonia (early-VAP, < 7 days) have decreased risk of methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa infections. We hypothesize that routinely using broad-spectrum antibiotics is unnecessary to treat trauma patients with the diagnosis of early-VAP., Methods: This retrospective cohort study included adult trauma patients with the diagnosis of VAP. The primary outcome was the presence of MRSA and/or P. aeruginosa in patients with early- and late-VAP. Secondary outcomes included the bacterial susceptibility of pathogens to methicillin, ampicillin/sulbactam, ceftriaxone, piperacillin/tazobactam, and cefepime. Intensive care unit (ICU) and hospital length of stay (LOS), ventilator-free days, and in-hospital mortality were also collected., Results: 164 patients met inclusion criteria, and 208 organisms (n = 90 early vs n = 118 late) were identified by respiratory culture. The incidence of MRSA and P. aeruginosa in early-VAP was 7.7% (7/90) and 5.6% (5/90), respectively. The susceptibility of bacteria causing early-VAP to ampicillin/sulbactam and ceftriaxone was 73.3% (66/90) and 83.3% (75/90), respectively. Ventilator-free days at 30 days was similar between groups ( P = .649). Patients with late-VAP spent more time in the ICU ( P = .040); however, in-hospital mortality was higher in the early-VAP group ( P = .012)., Conclusions: Ampicillin/sulbactam or ceftriaxone monotherapy did not provide reliable broad-spectrum coverage for early-VAP in our cohort. These findings highlight the importance of each institution performing a similar analysis to ensure adequate initial treatment of VAP., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Opioids remain the mainstay treatment of acute pain caused by trauma. The lack of evidence driven prescribing creates a challenging situation for providers. We hypothesized that the implementation of a trauma discharge opioid bundle (TDOB) would decrease the total morphine milligram equivalents (MME) prescribed at discharge while maintaining pain control., Methods: This was a pre-post study of adult trauma patients before and after implementation of a TDOB to guide the prescription of opioids and discharge prescription education in patients discharged from a level one trauma center. The pre-group and post-group, included consecutively discharged patients from September through November in 2018 and 2019. The primary outcome was the total MME prescribed at discharge., Results: A total of 377 patients met inclusion criteria. One hundred and fifty-one patients were included in the pre-group and 226 in the post-group. The total MME prescribed at discharge (225 ± [150-300] pre vs 200 ± [100-225] post, P = < .001) and maximum MME/day (45 ± [30-45] vs 30 ± [20-45], P = .004) were significantly less in the post-group. Incidence of outpatient refills within fourteen days were similar. More non-opioid pain adjuncts were prescribed post-intervention and discharge pain education was provided more frequently., Conclusion: The implementation of a TDOB significantly reduced the MME prescribed at discharge without increasing the number of opioid refills., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Importance: Sepsis and septic shock are major healthcare problems that need early and appropriate management., Objectives: To evaluate the association of daily cefepime pharmacokinetic/pharmacodynamic (PK/PD) parameters with change in Sequential Organ Failure Assessment (SOFA) score and vasopressors requirement., Design Setting and Participants: This is a retrospective study. Adult ICU patients who received cefepime for Gram-negative pneumonia or bloodstream infection (BSI) and had cefepime concentrations measured were included. Daily cefepime exposure was generated and PK/PD parameters calculated for patients. Repeated-measures mixed-effect modeling was used to evaluate the impact of PK/PD on the outcomes., Main Outcomes and Measures: Change in daily SOFA score and vasopressors requirement., Results: A total of 394 and 207 patients were included in the SOFA and vasopressors analyses, respectively. The mean (±sd) age was 55 years (19) and weight 81 kg (29). For the change in SOFA score, daily SOFA score, mechanical ventilation, renal replacement therapy, and number of vasopressors were included. In the vasopressors analysis, daily SOFA score, day of therapy, and hydrocortisone dose were significant covariates in the final model. Achieving cefepime concentrations above the minimum inhibitory concentration (MIC) (T >MIC ) for 100% of the dosing interval was associated with 0.006 µg/kg/min decrease in norepinephrine-equivalent dose. Cefepime PK/PD did not have an impact on the daily change in SOFA score., Conclusions and Relevance: Achieving 100% T >MIC was associated with negligible decrease in vasopressors requirement in ICU patients with Gram-negative pneumonia and BSI. There was no impact on the change in SOFA score., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Pediatric musculoskeletal infection can be a challenging clinical diagnosis. MRI protocols should be tailored appropriately to diagnose and localize sites of infection, to determine alternative pathologies that could explain the child's presentation, and to identify complications that could alter treatment or lead to devastating consequences in growing bones. In this review, we discuss MRI protocols tailored for suspected acute appendicular musculoskeletal infection in children. These protocols are based on patient age in order to generally reflect the developmental stage of the child, the corresponding relevant anatomy and physiology, and the skeletal maturity-dependent physiopathology of musculoskeletal infections., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Pharmacological venous thromboembolism (VTE) prophylaxis is recommended in the vast majority of trauma patients. The purpose of this study was to characterize current dosing practices and timing of initiation of pharmacological VTE chemoprophylaxis at trauma centers., Methods: This was an international, cross-sectional survey of trauma providers. The survey was sponsored by the American Association for the Surgery of Trauma (AAST) and distributed to AAST members. The survey included 38 questions about practitioner demographics, experience, level and location of trauma center, and individual/site-specific practices regarding the dosing, selection, and timing of initiation of pharmacological VTE chemoprophylaxis in trauma patients., Results: One hundred eighteen trauma providers responded (estimated response rate 6.9%). Most respondents were at level 1 trauma centers (100/118; 84.7%) and had >10 years of experience (73/118; 61.9%). While multiple dosing regimens were used, the most common dose reported was enoxaparin 30 mg every 12 hours (80/118; 67.8%). The majority of respondents (88/118; 74.6%) indicated adjusting the dose in patients with obesity. Seventy-eight (66.1%) routinely use antifactor Xa levels to guide dosing. Respondents at academic institutions were more likely to use guideline-directed dosing (based on the Eastern Association of the Surgery of Trauma and the Western Trauma Association guidelines) of VTE chemoprophylaxis compared with those at non-academic centers (86.2% vs 62.5%; p=0.0158) and guideline-directed dosing was reported more often if the trauma team included a clinical pharmacist (88.2% vs 69.0%; p=0.0142). Wide variability in initial timing of VTE chemoprophylaxis after traumatic brain injury, solid organ injury, and spinal cord injuries was found., Conclusions: A high degree of variability exists in prescribing and monitoring practices for the prevention of VTE in trauma patients. Clinical pharmacists may be helpful on trauma teams to optimize dosing and increase prescribing of guideline-concordant VTE chemoprophylaxis., Competing Interests: Competing interests: The research of JDS is supported by funding from the American the American College of Surgeons (George H. A. Clowes Memorial Research Career Development Award 2014–2019) and the National Institutes of Health (1 K08 GM109113-01). ERH reports research funding from the Patient-Centered Outcomes Research Institute (PCORI), the Agency for Healthcare Research and Quality (AHRQ), the National Institutes of Health National Heart, Lung, and Blood Institute (NIH/NHLBI), and the DOD/Army Medical Research Acquisition Activity. All other authors have no other financial disclosures regarding this topic., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There are persistent disparities in the delivery of cancer treatment, with Black patients receiving fewer of the recommended cancer treatment cycles than their White counterparts on average. To enhance racial equity in cancer care, innovative methods that apply antiracist principles to health promotion interventions are needed. The parent study for the current analysis, the Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) intervention, was a system-change intervention that successfully eliminated the Black-White disparity in cancer treatment completion among patients with early-stage breast and lung cancer. The intervention included specially trained nurse navigators who leveraged real-time data to follow-up with patients during their treatment journeys. Community and academic research partners conducted thematic analysis on all clinical notes (n = 3,251) written by ACCURE navigators after each contact with patients in the specialized navigation arm (n = 162). Analysis was informed by transparency and accountability, principles adapted from the antiracist resource Undoing Racism and determined as barriers to treatment completion through prior research that informed ACCURE. We identified six themes in the navigator notes that demonstrated enhanced accountability of the care system to patient needs. Underlying these themes was a process of enhanced data transparency that allowed navigators to provide tailored patient support. Themes include (1) patient-centered advocacy, (2) addressing system barriers to care, (3) connection to resources, (4) re-engaging patients after lapsed treatment, (5) addressing symptoms and side effects, and (6) emotional support. Future interventions should incorporate transparency and accountability mechanisms and examine the impact on racial equity in cancer care.

Background: Delirium occurs frequently in critically ill and injured patients and is associated with significant morbidity and mortality. Limited data exists on the risk factors for developing delirium in critically ill trauma patients and the effect of antipsychotic (AP) medications on delirium progression., Objective: The objective of this study is to determine the incidence of delirium in critically ill trauma versus non-trauma surgical patients and determine if the presence of trauma was associated with intensive care unit (ICU) delirium. Secondary outcomes included identifying risk factors for delirium and determining the impact of AP medication use on delirium progression in critically ill trauma patients., Methods: This retrospective review studies adult trauma/surgical ICU patients admitted between May 2017-July 2018 to a level I trauma and tertiary referral center. Regression modeling was used to determine the impact of AP use on delirium-free days., Results: Delirium was more common in critically ill trauma patients versus non-trauma surgical ICU patients [54/157 (34.4%) vs 42/270 (15.6%), P < .001]. Of the 54 trauma patients with delirium, 28 (52%) received an AP medication for delirium treatment and in the multiple linear regression analysis, AP use was significantly associated with fewer delirium-free days ( P = .02)., Discussion: Higher admission sequential organ failure assessment scores and increased length of stay were significantly associated with delirium onset in critically ill trauma patients. Use of AP medications for delirium treatment in this population had a negative impact on delirium-free days.

Objectives: To evaluate the association between early and cumulative beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) parameters and therapy outcomes in bloodstream infection (BSI)., Methods: Adult patients who received cefepime, meropenem, or piperacillin/tazobactam for BSI and had concentrations measured were included. Beta-lactam exposure was generated and the time that free concentration remained above the minimum inhibitory concentration (fT >MIC ) and four multiples of MIC (fT >4 × MIC ) were calculated for times 0-24 h and 0-7 days of therapy. Multiple regression analysis was performed to evaluate the impact of PK/PD on microbiological and clinical outcomes., Results: A total of 204 patients and 213 BSI episodes were included. The mean age was 58 years and weight 83 kg. Age, Sequential Organ Failure Assessment (SOFA) score, haemodialysis, Pitt bacteraemia score, and hours of empiric antibiotic therapy were significantly associated with certain outcomes and retained in the final model. In multiple regression analysis, fT >4 × MIC at 0-24 h and 0-7 days was a significant predictor of negative blood culture on day 7 (P=0.0161 and 0.0068, respectively). In the time-to-event analysis, patients who achieved 100% fT >4 × MIC at 0-24 h and 0-7 days had a shorter time to negative blood culture compared with those who did not (log-rank P=0.0004 and 0.0014, respectively). No significant associations were identified between PK/PD parameters and other outcomes, including improvement in symptoms at day 7 and 30-day mortality., Conclusion: Early and cumulative achievement of fT >4 × MIC was a significant predictor of microbiological outcome in patients with BSI., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

The coronavirus disease 2019 (COVID-19) pandemic continues to pose a significant threat to patients receiving advanced heart failure therapies. The current study was undertaken to better understand the relationship between obesity and outcomes of SARS-CoV-2 infection in patients with a left ventricular assist device (LVAD) or heart transplant. We performed a retrospective review of patients with a heart transplant or LVAD who presented to one of the participating 11 institutions between April 1 and November 30, 2020. Patients were grouped by body mass index (BMI) into obese (BMI ≥ 30 k/m2) and nonobese cohorts (BMI < 30 kg/m2). Multivariable logistic regression models were used to estimate effects of obesity on outcomes of interest. Across all centers, 162 heart transplant and 81 LVAD patients were identified; 54 (33%) and 38 (47%) were obese, respectively. Obese patients tended to have more symptoms at presentation. No differences in rates of hospitalization or ICU admission were noted. Obese patients with LVADs were more likely to require mechanical ventilation (39% vs. 8%, p < 0.05). No differences in renal failure or secondary infection were noted. Mortality was similar among heart transplant patients (11% [obese] vs. 16% [nonobese], p = 0.628) and LVAD patients (12% vs. 15%, p = 1.0). BMI was not associated with increased adjusted odds of mortality, ICU admission, or mechanical ventilation (all p > 0.10). In summary, acute presentations of SARS-CoV-2 among heart transplant and LVAD recipients carry a significantly higher mortality than the general population, although BMI does not appear to impact this. Further studies on the longer-term effects of COVID-19 on this population are warranted., (Copyright © ASAIO 2022.)

The COVID-19 pandemic exposed the consequences of systemic racism in the United States with Black, Hispanic, and other racial and ethnic diverse populations dying at disproportionately higher rates than White Americans. Addressing the social and health disparities amplified by COVID-19 requires in part restructuring of the healthcare system, particularly the diversity of the healthcare workforce to better reflect that of the US population. In January 2021, the Association of Black Cardiologists hosted a virtual roundtable designed to discuss key issues pertaining to medical workforce diversity and to identify strategies aimed at improving racial and ethnic diversity in medical school, graduate medical education, faculty, and leadership positions. The Nurturing Diverse Generations of the Medical Workforce for Success with Authenticity roundtable brought together diverse stakeholders and champions of diversity and inclusion to discuss innovative ideas, solutions, and opportunities to address workforce diversification.

Clonal hematopoiesis of indeterminate potential (CHIP) is common both in healthy individuals and patients with hematological cancers. Recent studies have showed worse prognosis for patients with multiple myeloma (MM) and non-Hodgkin lymphoma undergoing stem cell transplant, that have concomitant presence of CHIP. Data regarding the clinical and biological role of CHIP in plasma cell dyscrasias (PCDs) is rapidly increasing. However, the prevalence and prognostic implication of CHIP in patients with MM outside of the transplant setting, and in those with other more indolent PCDs remains elusive. Here we explored the prevalence and clinical implications of CHIP detected through next-generation sequencing in 209 patients with PCDs including MM, light chain (AL) amyloidosis (ALA), monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM). To avoid attributing the mutations to the plasma cell clone, CHIP was defined as the presence of DNMT3A, TET2, or ASXL1 mutations in the peripheral blood or bone marrow (DTA-CH). The prevalence of DTA-CH was 19% in patients with PCDs, with no difference between each PCD. TET2 (23%) and DNMT3A (22%), were the most frequently mutated genes. DTA-CH correlated with older age in MM (P = .001) and MGUS/SMM (P = 0.0007), as well as with coronary artery disease or congestive heart failure in MM (P = .03). DTA-CH did not predict worse OS or PFS in either MM or ALA, nor it predict higher risk of progression to MM in patients with MGUS/SMM. Our results overall further elucidate the prevalence and mutational spectrum of CHIP in PCDs, providing more information regarding the clinical relevance of CHIP in this patient population., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Keeping abreast with current literature can be challenging, especially for practitioners caring for patients sustaining thermal or inhalation injury. Practitioners caring for patients with thermal injuries publish in a wide variety of journals, which further increases the complexity for those with resource limitations. Pharmacotherapy research continues to be a minority focus in primary literature. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Sixteen geographically dispersed, board-certified pharmacists participated in the review. A MeSH-based, filtered search returned 1536 manuscripts over the previous 2-year period. After manual review and exclusions, only 98 (6.4%) manuscripts were determined to have a potential impact on current pharmacotherapy practices and included in the review. A summary of the 10 articles that scored highest are included in the review. Nearly half of the reviewed manuscripts were assessed to lack a significant impact on current practice. Despite an increase in published literature over the previous 2-year review, the focus and quality remain unchanged. There remains a need for investment in well-designed, high impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Early detection and characterization of increased left ventricular (LV) wall thickness can markedly impact patient care but is limited by under-recognition of hypertrophy, measurement error and variability, and difficulty differentiating causes of increased wall thickness, such as hypertrophy, cardiomyopathy, and cardiac amyloidosis., Objective: To assess the accuracy of a deep learning workflow in quantifying ventricular hypertrophy and predicting the cause of increased LV wall thickness., Design, Settings, and Participants: This cohort study included physician-curated cohorts from the Stanford Amyloid Center and Cedars-Sinai Medical Center (CSMC) Advanced Heart Disease Clinic for cardiac amyloidosis and the Stanford Center for Inherited Cardiovascular Disease and the CSMC Hypertrophic Cardiomyopathy Clinic for hypertrophic cardiomyopathy from January 1, 2008, to December 31, 2020. The deep learning algorithm was trained and tested on retrospectively obtained independent echocardiogram videos from Stanford Healthcare, CSMC, and the Unity Imaging Collaborative., Main Outcomes and Measures: The main outcome was the accuracy of the deep learning algorithm in measuring left ventricular dimensions and identifying patients with increased LV wall thickness diagnosed with hypertrophic cardiomyopathy and cardiac amyloidosis., Results: The study included 23 745 patients: 12 001 from Stanford Health Care (6509 [54.2%] female; mean [SD] age, 61.6 [17.4] years) and 1309 from CSMC (808 [61.7%] female; mean [SD] age, 62.8 [17.2] years) with parasternal long-axis videos and 8084 from Stanford Health Care (4201 [54.0%] female; mean [SD] age, 69.1 [16.8] years) and 2351 from CSMS (6509 [54.2%] female; mean [SD] age, 69.6 [14.7] years) with apical 4-chamber videos. The deep learning algorithm accurately measured intraventricular wall thickness (mean absolute error [MAE], 1.2 mm; 95% CI, 1.1-1.3 mm), LV diameter (MAE, 2.4 mm; 95% CI, 2.2-2.6 mm), and posterior wall thickness (MAE, 1.4 mm; 95% CI, 1.2-1.5 mm) and classified cardiac amyloidosis (area under the curve [AUC], 0.83) and hypertrophic cardiomyopathy (AUC, 0.98) separately from other causes of LV hypertrophy. In external data sets from independent domestic and international health care systems, the deep learning algorithm accurately quantified ventricular parameters (domestic: R2, 0.96; international: R2, 0.90). For the domestic data set, the MAE was 1.7 mm (95% CI, 1.6-1.8 mm) for intraventricular septum thickness, 3.8 mm (95% CI, 3.5-4.0 mm) for LV internal dimension, and 1.8 mm (95% CI, 1.7-2.0 mm) for LV posterior wall thickness. For the international data set, the MAE was 1.7 mm (95% CI, 1.5-2.0 mm) for intraventricular septum thickness, 2.9 mm (95% CI, 2.4-3.3 mm) for LV internal dimension, and 2.3 mm (95% CI, 1.9-2.7 mm) for LV posterior wall thickness. The deep learning algorithm accurately detected cardiac amyloidosis (AUC, 0.79) and hypertrophic cardiomyopathy (AUC, 0.89) in the domestic external validation site., Conclusions and Relevance: In this cohort study, the deep learning model accurately identified subtle changes in LV wall geometric measurements and the causes of hypertrophy. Unlike with human experts, the deep learning workflow is fully automated, allowing for reproducible, precise measurements, and may provide a foundation for precision diagnosis of cardiac hypertrophy.

The COVID-19 pandemic underscored our healthcare system's unpreparedness to manage an unprecedented pandemic. Heart failure (HF) physicians from 14 different academic and private practice centers share their systems' challenges and innovations to care for patients with HF, heart transplantation, and patients on LVAD support during the COVID-19 pandemic. We discuss measures implemented to alleviate the fear in seeking care, ensure continued optimization of guideline directed medical therapy (GDMT), manage the heart transplant waiting list, continue essential outpatient monitoring of anticoagulation in LVAD patients and surveillance testing post-heart transplant, and prevent physician burnout. This collaborative work can build a foundation for better preparation in the face of future challenges., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Improving cancer survival represents the most significant effect of precision medicine and personalized molecular and immunologic therapeutics. Cardiovascular health becomes henceforth a key determinant for the direction of overall outcomes after cancer. Comprehensive tissue diagnostic studies undoubtedly have been and continue to be at the core of the fight against cancer. Will a systemic approach integrating circulating blood-derived biomarkers, multimodality imaging technologies, strategic panomics, and real-time streams of digitized physiological data overcome the elusive cardiovascular tissue diagnosis in cardio-oncology? How can such a systemic approach be personalized for application in day-to-day clinical work, with diverse patient populations, cancer diagnoses, and therapies? To address such questions, this scientific statement approaches a broad definition of the biomarker concept. It summarizes the current literature on the utilization of a multitude of established cardiovascular biomarkers at the intersection with cancer. It identifies limitations and gaps of knowledge in the application of biomarkers to stratify the cardiovascular risk before cancer treatment, monitor cardiovascular health during cancer therapy, and detect latent cardiovascular damage in cancer survivors. Last, it highlights areas in biomarker discovery, validation, and clinical application for concerted efforts from funding agencies, scientists, and clinicians at the cardio-oncology nexus.

The abundance of literature documenting the impact of racism on health disparities requires additional theoretical, statistical, and conceptual contributions to illustrate how anti-racist interventions can be an important strategy to reduce racial inequities and improve population health. Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) was an NIH-funded intervention that utilized an antiracism lens and community-based participatory research (CBPR) approaches to address Black-White disparities in cancer treatment completion. ACCURE emphasized change at the institutional level of healthcare systems through two primary principles of antiracism organizing: transparency and accountability. ACCURE was successful in eliminating the treatment completion disparity and improved completion rates for breast and lung cancer for all participants in the study. The structural nature of the ACCURE intervention creates an opportunity for applications in other health outcomes, as well as within educational institutions that represent social determinants of health. We are focusing on the maternal healthcare and K-12 education systems in particular because of the dire racial inequities faced by pregnant people and school-aged children. In this article, we hypothesize cross-systems translation of a system-level intervention exploring how key characteristics of ACCURE can be implemented in different institutions. Using core elements of ACCURE (i.e., community partners, milestone tracker, navigator, champion, and racial equity training), we present a framework that extends ACCURE's approach to the maternal healthcare and K-12 school systems. This framework provides practical, evidence-based antiracism strategies that can be applied and evaluated in other systems to address widespread structural inequities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Baker, Black, Dixon, Yongue, Mason, McCarter, Manning, Hessmiller, Griesemer, Garikipati, Eng, Bullock, Bosire, Alexander and Lightfoot.)

Background: An electrocardiogram (ECG) is a simple and cheap non-invasive tool that shows various abnormalities and has prognostic value for patients with light-chain amyloidosis (AL). The present study aimed to explore the association between ECG characteristics and cardiac magnetic resonance (CMR)-detected amyloid burden and to investigate the prognostic value of ECG in AL amyloidosis. Methods: We prospectively enrolled 99 patients with AL amyloidosis (56 male patients; median age, 58 y). Detailed clinical information, 12-lead ECG, and CMR data were collected. All patients were followed up longitudinally, and the endpoint was all-cause mortality. ECG characteristics were analyzed and correlated with the degree of late gadolinium enhancement (LGE) and extracellular volume (ECV) by T1 mapping on CMR. The prognostic value of ECG characteristics was analyzed using Kaplan-Meier survival analysis and multivariate Cox regression. Results: During a median follow-up period of 33 months, 69 of the 99 patients died. Fragmented Q wave-R wave-S wave (QRS), pathological Q waves, the Sokolow index, QRS duration, and voltages were significantly associated with the extent of LGE, native T1, and ECV by CMR ( p < 0.05). Fragmented QRS and Sokolow index showed independent prognostic value in AL amyloidosis ( p = 0.001; p = 0.026, respectively). Fragmented QRS remained independent after adjusting for clinical values (hazard ratio: 2.034; 95% confidence interval: 1.148-3.603; p = 0.015). However, no ECG characteristics were independent predictors for prognosis in AL amyloidosis when LGE and ECV were included in the multivariate analysis. Conclusion: ECG abnormalities showed significant association with CMR indicators of amyloid burden. Fragmented QRS has an independent prognostic value in AL amyloidosis and could be used as an alternative marker when CMR is not available., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Guo, Chen, Wan, Song, Yang, Xu, Zhang, Alexander, Han and Chen.)

Competing Interests: Dr Alexander is supported the American Heart Association-Amos Medical Faculty Development Program (19AMFDP34990036) and the National Center for Advancing Translational Sciences of the National Institutes of Health under award number KL2TR003143; has received an investigator-initiated research grant from Pfizer; and has received consulting fees (modest) from Alnylam, Eidos, and Pfizer. Dr Nguyen has reported that he has no relationships relevant to the contents of this paper to disclose.

Background: COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear., Methods: We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant., Results: The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy., Conclusions: We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients., (Copyright © 2021 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Herpes simplex virus (HSV) is common in the population and reactivation of latent infection often occurs in times of physiologic stress, including postburn injury. Active HSV infection complicates burn injury recovery and increases morbidity. A retrospective chart review of high-risk burn patients (≥20%TBSA and/or facial burns) who had screening HSV immunoglobulin titers drawn from 2015 to 2018 was conducted. Titer levels and morbidity-related outcomes were compared between patients who developed active infection and those who did not. Fifty-six patients had serum HSV titers measured. Twenty-nine patients (52%) developed clinical signs of HSV infection, almost all of which (97%) suffered facial burns. Titers were ordered on median hospital day 1.5 (0.00-4.0) and infection occurred on day 8.0 (2.0-16). Median HSV-1,2 IgM titers were significantly increased in patients who developed clinically active HSV infection (0.71 [0.44-1.1] vs 0.52 [0.34-0.74], P = .02). Median HSV-1 IgG (P = .65) and HSV-2 IgG titers (P = .97) were not different between groups. Patients who developed active infection had a comparable hospital length of stay (27 [9.5-40] days vs 20 [8.0-28] days, P = .17) and ICU length of stay (26 [13-49] days vs 19 [11-27] days, P = .09) to those who did not develop infection. There was no difference in mortality. Increased HSV-1 and 2 IgM screening levels were associated with an increased risk of developing active HSV infection, and offer a specific screening modality in high-risk patients. Elevated IgM titers warrant further consideration for administration of HSV prophylaxis, as earlier intervention may prevent infection onset and minimize morbidity., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)