bluuebunny/crossref_metadata_2025 huggingface dataset:
Prophylactic and early outpatient treatment of COVID-19 in patients with kidney disease: considerations from the Immunonephrology Working Group of the European Renal Association (ERA-IWG)
Authors: Hilhorst Marc , Bemelman Frederike J , Bruchfeld Annette , Fernandez-Juarez Gema M , Floege Jürgen , Frangou Eleni , Goumenos Dimitrios , van Kooten Cees , Kronbichler Andreas , Stevens Kate I , Turkmen Kultigin , Wiersinga W Joost , Anders Hans-Joachim
Published: March 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients.
VILLIN2 regulates cotton defense againstVerticillium dahliaeby modulating actin cytoskeleton remodeling
Authors: Li Wen-Bo , Song Shuang-Wei , Zhong Meng-Meng , Liu Lan-Gong , Su Lei , Han Li-Bo , Xia Gui-Xian , Sun Yong-Duo , Wang Hai-Yun
Published: March 2023

The active structural change of actin cytoskeleton is a general host response upon pathogen attack. This study characterized the function of the cotton (Gossypium hirsutum) actin-binding protein VILLIN2 (GhVLN2) in host defense against the soilborne fungus Verticillium dahliae. Biochemical analysis demonstrated that GhVLN2 possessed actin-binding, -bundling, and -severing activities. A low concentration of GhVLN2 could shift its activity from actin bundling to actin severing in the presence of Ca2+. Knockdown of GhVLN2 expression by virus-induced gene silencing reduced the extent of actin filament bundling and interfered with the growth of cotton plants, resulting in the formation of twisted organs and brittle stems with a decreased cellulose content of the cell wall. Upon V. dahliae infection, the expression of GhVLN2 was downregulated in root cells, and silencing of GhVLN2 enhanced the disease tolerance of cotton plants. The actin bundles were less abundant in root cells of GhVLN2-silenced plants than in control plants. However, upon infection by V. dahliae, the number of actin filaments and bundles in the cells of GhVLN2-silenced plants was raised to a comparable level as those in control plants, with the dynamic remodeling of the actin cytoskeleton appearing several hours in advance. GhVLN2-silenced plants exhibited a higher incidence of actin filament cleavage in the presence of Ca2+, suggesting that pathogen-responsive downregulation of GhVLN2 could activate its actin-severing activity. These data indicate that the regulated expression and functional shift of GhVLN2 contribute to modulating the dynamic remodeling of the actin cytoskeleton in host immune responses against V. dahliae.
A comparison of the assessments used in campus-based years at the College of Medicine, Imam Abdulrahman Bin Faisal University, Saudi Arabia
Authors: Latif Rabia , Alsunni Ahmed A
Published: March 2023

Study Purpose

Multiple assessment tools are used to assess future doctors’ knowledge, clinical skills, and professional attitudes. In the present research, the difficulty level and discriminating ability of different types of written and performance-based assessments designed to measure the knowledge and competency of medical students were compared.

Methods

The assessment data of 2nd & 3rd-year medical students (the academic year 2020-2021) in the College of Medicine at Imam Abdulrahman Bin Faisal University (IAU) were retrospectively reviewed. Based on end-of-the-year overall grades, students were divided into high and low scorers. Both groups were compared by independent sample t-test for their mean scores achieved in each type of assessment. Difficulty level and discriminating ability of the assessments were also explored. MS Excel and Statistical Package for Social Sciences (SPSS version 27) were used for analysis. Area under the curve was calculated through ROC analysis. A p-value <0.05 was believed significant.

Results

In each type of written assessment, the high scorer group achieved significantly higher scores compared to the low scorers. Among performance-based assignments (except the PBLs), scores did not differ significantly between high and low scorers. The difficulty level of performance-based assessments was “easy” whereas it was “moderate” for written assessments (except the OSCE). The discriminating ability of performance-based assessments was “poor” whereas it was “moderate/excellent” for written assessments (except the OSCE).

Conclusion

Our study results indicate that written assessments have excellent discriminatory ability. However, performance-based assessments are not as difficult and discriminatory as written assessments. The PBLs are relatively discriminatory among all performance-based assessments.

Key messages What is already known on this topic At Imam Abdulrahman Bin Faisal University, written and performance-based assessments both are graded on criterion-referenced scales. The student’s grades at the end of the year are an aggregate of his/her scores in written and performance-based assessments. What this study adds Our study results show that performance-based assessments are not as difficult and discriminatory in differentiating between high and low scorers as written assessments. How this study might affect research, practice or policy Performance-based assessments should be made a hurdle exam (pass or fail) for the students to move to the next level, or students must pass each assessment component (written and performance-based) separately.
Health Care Professionals’ Decision Making Related to Mobility and Safety for People in the Hospital: A Scoping Review
Authors: Bainbridge Liz , Fary Robyn E , Briffa Kathy , Hill Keith D , Burton Elissa
Published: March 2023

Objective

Mobility dysfunction can have an impact on safety, and this fact is particularly relevant to hospital settings. There are no clear standards for how health care professionals should approach the aim to encourage mobility without compromising safety. The objective of this scoping review was to identify factors that shape health care professionals’ decision making for people in hospitals, in situations in which mobility and safety are taken into consideration.

Methods

For this scoping review, 4 databases (Medline, CINAHL, PubMed, and Scopus) were searched. Terms previously agreed upon were used to identify peer-reviewed articles related to decision making by health care professionals in hospital settings (acute and rehabilitation), in which safety and mobility were factors for consideration. An initial screening of titles and abstracts was conducted by a single reviewer. Two reviewers independently screened the full texts of the remaining articles. The key findings of the articles were synthesized to determine common themes.

Results

After 10,717 articles were screened, 28 met the inclusion criteria. Ten themes influencing decision making were identified: Clinical factors assessed; health care professional experience; limited use of standardized tests; impact of institutional governance; risk/benefit trade-off; capacity for decision making; role of the multidisciplinary team; families and others; communication; and fear of negative outcomes.

Conclusion

A wide range of factors influence health care professionals’ decision making. The decisions can be complex, and individual priorities may vary in the balancing of safety with promotion of independence. Health care professionals rely on experience, clinical judgment, and shared decision making.

Impact

This review brings attention to many factors that contribute to decision making when mobility and safety are the factors. Health care professionals should include patients’ values and monitor the impact of their personal preferences on this process.
Association between being breastfed and cardiovascular disease: a population cohort study of 320 249 participants
Authors: Nakada Shinya , Ho Frederick K , Celis-Morales Carlos , Pell Jill P
Published: March 2023

Background

Being breastfed is associated with lower cardiovascular risk factors but, to date, no studies have demonstrated a protective effect on cardiovascular disease (CVD). This study aims to address the limitations of previous studies, specifically insufficient statistical power and residual confounding, to determine if such association exists.

Methods

This is a population-based retrospective cohort study of 320 249 men and women aged 40–69 years. Breastfeeding status was self-reported. CVD and myocardial infarction (MI) events and deaths based via linkage to hospitalization and death records.

Results

Overall, 28 469 (8.4%) participants experienced a CVD event and 5174 (1.6%) experienced an MI. Following adjustment for sociodemographic, lifestyle and early life confounders, breastfeeding was associated with a reduced risk of CVD events (HR 0.97, 95% CI 0.94–1.00, P = 0.041), CVD deaths (HR 0.91, 95% CI 0.84–0.98, P = 0.017), MI events (HR 0.93, 95% CI 0.87–0.99, P = 0.033) and MI deaths (HR 0.81, 95% CI 0.67–0.98, P = 0.026).

Conclusions

Child health benefits of breastfeeding are well established. However, the benefits of breastfeeding may extend into later life reinforcing the need to encourage and support breastfeeding.
Collagen-based injectable and self-healing hydrogel with multifunction for regenerative repairment of infected wounds
Authors: Gu Haojie , Li Han , Wei Liren , Lu Jian , Wei Qingrong
Published: March 2023

At present, the development trend of dressing materials is being multifunctional for convenient and long-term nursing care process of some complicated wounds. Here, basing on the theory of wound moist healing, an injectable and self-healing hydrogel comprising of collagen (COL), chitosan (CS) and oxidation modified Konjac glucomannan (OKGM), which acts as a macromolecular cross-linker to construct dynamic Schiff-base bonds was smartly designed. The strategy of introducing the silver nanoparticles (Ag NPs) into the COL–CS–OKGM hydrogel matrix achieved a markedly enhanced antibacterial activity derived from the synergistical effect between the Ag+ and the mild photothermal efficacy of Ag NPs, which also improved the local capillary blood circulation of the wound area to further facilitate wound healing process. The excellent syringeability and self-healing behaviors endowed the COL–CS–OKGM–Ag hydrogel with self-adapting ability for the wounds with irregular and large area needing frequent applying and changing without secondary injuries. In vitro and in vivo evaluations verified that so-designed COL–CS–OKGM–Ag hydrogel also with hemostatic performance is a promising multifunctional dressing for the treatments of infected wound with not only good biocompatibility and convenient use, but also with desired regenerative healing prognoses benefited from hydrogel moist environment and physiotherapy.
Into the Trees: Random Forests for Predicting Fusarium Head Blight Epidemics of Wheat in the United States
Authors: Shah Denis A. , De Wolf Erick D. , Paul Pierce A. , Madden Laurence V.
Published: March 2023

Constructing models that accurately predict Fusarium head blight (FHB) epidemics and are also amenable to large-scale deployment is a challenging task. In the United States, the emphasis has been on simple logistic regression (LR) models, which are easy to implement but may suffer from lower accuracies when compared with more complicated, harder-to-deploy (over large geographies) model frameworks such as functional or boosted regressions. This article examined the plausibility of random forests (RFs) for the binary prediction of FHB epidemics as a possible mediation between model simplicity and complexity without sacrificing accuracy. A minimalist set of predictors was also desirable rather than having the RF model use all 90 candidate variables as predictors. The input predictor set was filtered with the aid of three RF variable selection algorithms (Boruta, varSelRF, and VSURF), using resampling techniques to quantify the variability and stability of selected variable sets. Post-selection filtering produced 58 competitive RF models with no more than 14 predictors each. One variable representing temperature stability in the 20 days before anthesis was the most frequently selected predictor. This was a departure from the prominence of relative humidity-based variables previously reported in LR models for FHB. The RF models had overall superior predictive performance over the LR models and may be suitable candidates for use by the Fusarium Head Blight Prediction Center.
A Machine Learning Approach to Developing an Accurate Prediction of Maximal Heart Rate During Exercise Testing in Apparently Healthy Adults
Authors: Cundrič Larsen , Bosnić Zoran , Kaminsky Leonard A. , Myers Jonathan , Peterman James E. , Markovic Vidan , Arena Ross , Popović Dejana
Published: March 2023

Purpose:

Maximal heart rate (HRmax) continues to be an important measure of adequate effort during an exercise test. The aim of this study was to improve the accuracy of HRmax prediction using a machine learning (ML) approach.

Methods:

We used a sample from the Fitness Registry of the Importance of Exercise National Database, which included 17 325 apparently healthy individuals (81% males) who performed a maximal cardiopulmonary exercise test. Two standard formulas for HRmax prediction were tested: Formula1 = 220 − age (yr), root-mean-squared error (RMSE) 21.9, relative root-mean-squared error (RRMSE) 1.1; and Formula2 = 209.3 − 0.72 × age (yr), RMSE 22.7 and RRMSE 1.1. For ML model prediction, we used age, weight, height, resting HR, and systolic and diastolic blood pressure. The following ML algorithms to predict HRmax were applied: lasso regression (LR), neural networks (NN), support vector machine (SVM) and random forests (RF). An evaluation was performed using cross-validation and by computing the RMSE and RRMSE, Pearson correlation, and Bland-Altman plots. The best predictive model was explained with Shapley Additive Explanations (SHAP).

Results:

The HRmax for the cohort was 162 ± 20 bpm. All ML models improved HRmax prediction and reduced RMSE and RRMSE compared with Formula1 (LR: 20.2%, NN: 20.4%, SVM: 22.2%, and RF: 24.7%). The predictions of all algorithms significantly correlated with HRmax (r = 0.49, 0.51, 0.54, 0.57, respectively; P < .001). Bland-Altman analysis demonstrated lower bias and 95% CI for all ML models in comparison with standard equations. The SHAP explanation showed a high impact of all selected variables.

Conclusions:

Machine learning, particularly the RF model, improved prediction of HRmax using readily available measures. This approach should be considered for clinical application to refine HRmax prediction.
Acute Sterile Keratolysis After Deep Anterior Lamellar Keratoplasty in a Patient With Keratoconus: A Case Report
Authors: Al-Swailem Samar A. , AlHilali Sara , Maktabi Azza M. Y.
Published: March 2023

Purpose:

The purpose of this study was to report the outcomes of using gamma-irradiated sterile cornea (GISC) as a deep lamellar keratoplasty (DALK) graft in a patient with keratoconus.

Methods:

This is a case report.

Results:

A 33-year-old male patient diagnosed with keratoconus underwent DALK using a GISC and developed a persistent epithelial defect which eventually led to sterile keratolysis necessitating further surgical interventions. Management and slitlamp photography, anterior segment optical coherence tomography (AS-OCT), and histopathological examination of the explanted graft are described in detail.

Conclusions:

This is the first reported case of sterile keratolysis after the use of GISC lenticule in DALK in a healthy patient with keratoconus. The underlying pathophysiology is not clearly understood, and some theories have been proposed in this report. Surgeons need to be aware of this rare complication and are encouraged to have a low threshold for graft replacement to ensure good clinical and visual outcomes. Developing a prospective complication registry to document complications after the use of GISC lenticules in ophthalmic surgery is recommended.
Pitfalls and Possibilities of Ventricular Assist Device Support in Congenitally Corrected Transposition of the Great Arteries in Children
Authors: Belfiore Alyssa , Maurich Andrea , Honjo Osami , Mazwi Mjaye , Jean-St-Michel Emilie , Deng Mimi , Lynch Aine , Zaulan Oshri , Jeewa Aamir
Published: March 2023

Congenitally corrected transposition of the great arteries (ccTGAs) represents a complex form of congenital heart disease that is associated with several cardiac complications. Herein is a case series of three children with ccTGA and ventricular assist device (VAD) inserted for systemic right ventricle failure at a single institution. All patients remained hemodynamically stable postimplant and were successfully discharged from the intensive care unit to undergo postoperative rehabilitation. All three patients received an orthotopic heart transplant with uneventful posttransplant courses. This case series provides insight into the medical management and technical feasibility of VAD support in children with ccTGA with end-stage heart failure.
A Landscape Analysis of Prevention of Vertical Transmission Program Data and Interventions From Fiscal Years 2019–2021
Authors: Okegbe Tishina , Amzel Anouk , Gunnala Rajni , Abuelgasim Khalda , Traub Ariana , Lenka Matjeko , Mirembe Justine , Thuku Jeri , Rurangwa Aimee ,   USAID/PEPFAR Preventing Vertical Transmission (PVT) Group
Published: March 2023

Introduction:

In 2020, an estimated 150,000 infants acquired HIV infection through vertical transmission. With pregnant and breastfeeding women facing numerous social and health system barriers, continuity of care for mother–infant pairs (MIPs) requires prioritized engagement for timely infant HIV testing and linkage to treatment.

Methods:

PEPFAR Monitoring, Evaluation, and Reporting indicators were analyzed from across 14 USAID-supported countries across 3 fiscal years (FYs) (October 2018–September 2021): number of HIV-exposed infants (HEIs) with a sample collected for an HIV test by age 2 months, percentage of HEI who received an HIV test by age 2 months (EID 2 mo coverage), and final outcome status of HEIs. Qualitative information on implementation of PVT interventions was gathered using a structured survey disseminated to USAID/PEPFAR country teams.

Results:

From October 2018 to September 2021, 716,383 samples were collected for infant HIV tests. EID 2 mo coverage increased across the FYs from 77.3% in FY19% to 83.5% in FY21. Eswatini, Lesotho, and South Africa demonstrated the highest EID 2 mo coverage across all 3 FYs. Burundi (93.6%), DRC (92%), and Nigeria (90%) had the highest percentage of infants with a known final HIV outcome. Qualitative survey data showed that the most implemented interventions used by the countries were mentor mothers, appointment reminders, cohort registers, and joint provision of MIP services.

Conclusions:

Achieving eVT requires a client-centered and multipronged approach, typically combining several PVT interventions. Country and program implementers should use person-centered solutions to best target MIPs to be retained in the continuum of care.
Food and Water Insecurity in Sexual and Gender Minority Groups Living With HIV in Lagos, Nigeria
Authors: Hamill Matthew M. , Hu Fengming , Adebajo Sylvia , Kokogho Afoke , Tiamiyu Abdulwasiu B. , Parker Zahra F. , Charurat Manhattan E. , Ake Julie A. , Baral Stefan D. , Nowak Rebecca G. , Crowell Trevor A. ,   for the TRUST/RV368 Study Group
Published: March 2023

Background:

Food and water insecurity are associated with poor health outcomes that may be exacerbated by social marginalization and barriers to health care experienced by sexual and gender minorities (SGM) in resource-limited settings. We explored factors associated with food and water insecurity in SGM with HIV.

Setting:

A longitudinal study of 357 men who have sex with men, transgender women, and other gender-identifying people in Lagos, Nigeria.

Methods:

Laboratory testing, interviews, food and water assessments, and anthropometry were performed quarterly. Robust Poisson regression with generalized estimating equations was used to evaluate factors potentially associated with food and water insecurity.

Results:

From 2014 to 2018, 357 SGM with HIV completed either the food or water assessments. At baseline, participants identified as cisgender men who have sex with men 265 (74.2%), transgender women 63 (17.7%), or as nonbinary/other gender 29 (8.1%). Food insecurity and water insecurity were reported by 63/344(18.3%) and 113/357(31.7%), respectively, at any visit. Food and water insecurity each decreased with ongoing study participation. Food insecurity was associated with nonpartnered relationship status, CD4 count <500 cells/mm3, and lack of access to piped water. Water insecurity was associated with age 25 years or older, living with a man, transactional sex, and food insecurity.

Conclusions:

Food and water insecurity were common among SGM in Nigeria and decreased with continued study participation, suggesting amenability to intervention when SGM are successfully engaged in care. Targeted interventions to support food and water security may improve HIV-related outcomes, such as CD4 count.
2-[18F]FDG PET/CT Flare-up Phenomena Following T-Cell Engager Bispecific Antibody in Multiple Myeloma
Authors: Jamet Bastien , Bodet-Milin Caroline , Moreau Philippe , Kraeber-Bodéré Françoise , Touzeau Cyrille
Published: March 2023

T-cell–redirecting bispecific antibodies represent a new standard of care for the treatment of triple-class refractory myeloma patients. Here, 2-[18F]FDG PET/CT imaging was performed on a 61-year-old woman with relapsed myeloma to determine metabolic response to talquetamab, a GPRC5DxCD3-bispecific antibody. At day 28, monoclonal (M) component assessment confirmed very good partial response (97% monoclonal protein reduction), whereas 2-[18F]FDG PET/CT imaging revealed early bone flare-up phenomena. At day 84, bone marrow aspirate, M-component assessment, and 2-[18F]FDG PET/CT demonstrated complete response, confirming the early flare-up hypothesis.
Increased Petrous Bone Uptake on 18F-PSMA-1007 PET/CT Due to Otospongiosis
Authors: Neveü Sophie , Becker Minerva , Guinand Nils , Mainta Ismini Charis , Lenoir Vincent
Published: March 2023

We report the case of a 74-year-old man who had undergone radical prostatectomy for prostatic cancer 6 months earlier. Elevated prostate-specific antigen during follow-up prompted 18F–prostate-specific membrane antigen (PSMA) ligand PET/CT (18F-PSMA-1007 PET/CT) to search for new manifestations of prostate cancer, revealing an increased focal uptake (SUVmax, 5.9) in the left cochlear/pericochlear temporal bone and equivocal PSMA-RADS-3a external iliac nodes. Comparison with cone-beam CT and MRI showed that the focal temporal bone uptake corresponded to the typical morphological features of active otospongiosis (otosclerosis) in the context of a previously known long-standing otospongiosis.
Uncommon Manifestation of Oligometastatic Prostate Cancer
Authors: Luna Cibele , Kryvenko Oleksandr N. , Martinez Jose , Singal Rakesh , Kuker Russ
Published: March 2023

A 76-year-old man with a history of prostate cancer diagnosed in 2008 developed biochemical recurrence in 2010 and started intermittent androgen deprivation therapy. In 2021, due to rising prostate-specific antigen, an 18F-piflufolastat PSMA PET/CT was performed. It showed a radiotracer-avid sclerotic lesion in the right iliac bone and an indeterminate radiotracer-avid nodule in the umbilical region, demonstrating progressive enlargement and increased uptake on subsequent imaging. Pathologic analysis of the umbilical nodule revealed metastatic prostate cancer—a finding eponymically referred to as a Sister Mary Joseph nodule.
Health Care Simulation as a Training Tool for Epidemic Management
Authors: Corvetto Marcia A. , Altermatt Fernando R. , Belmar Francisca , Escudero Eliana
Published: March 2023

Summary Statement

The objective of this research was to identify and review studies that have evaluated the impact of simulation-based training on health care professionals during epidemics.

All studies in health care simulation-based training published during the last 5 epidemics with a global impact (SARS-CoV, H1N1, MERS, Ebola, SARS-CoV-2; through July 2021) were selected from a systematic search of PUBMED, EMBASE, and key journals.

The search strategy identified 274 studies; 148 met the inclusion criteria and were included. Most of the studies were developed in response to SARS-CoV-2 infection (n = 117, 79.1%), used a descriptive approach (n = 54, 36.5%), and were used to train technical skills (n = 82, 55.4%).

This review demonstrates a growing interest in publications related to health care simulation and epidemics. Most of the literature is marked by limited study designs and outcome measurements, although there is a trend toward the use of more refined methodologies in the most recent publications. Further research should seek the best evidence-based instructional strategies to design training programs in preparation for future outbreaks.
Current patterns of trauma center proliferation have not led to proportionate improvements in access to care or mortality after injury: An ecologic study
Authors: Amato Stas , Benson Jamie S. , Stewart Barclay , Sarathy Ashwini , Osler Turner , Hosmer David , An Gary , Cook Alan , Winchell Robert J. , Malhotra Ajai K.
Published: March 2023

BACKGROUND

Timely access to high-level (I/II) trauma centers (HLTCs) is essential to minimize mortality after injury. Over the last 15 years, there has been a proliferation of HLTC nationally. The current study evaluates the impact of additional HLTC on population access and injury mortality.

METHODS

A geocoded list of HLTC, with year designated, was obtained from the American Trauma Society, and 60-minute travel time polygons were created using OpenStreetMap data. Census block group population centroids, county population centroids, and American Communities Survey data from 2005 and 2020 were integrated. Age-adjusted nonoverdose injury mortality was obtained from CDC Wide-ranging Online Data for Epidemiologic Research and the Robert Wood Johnson Foundation. Geographically weighted regression models were used to identify independent predictors of HLTC access and injury mortality.

RESULTS

Over the 15-year (2005–2020) study period, the number of HLTC increased by 31.0% (445 to 583), while population access to HLTC increased by 6.9% (77.5–84.4%). Despite this increase, access was unchanged in 83.1% of counties, with a median change in access of 0.0% (interquartile range, 0.0–1.1%). Population-level age-adjusted injury mortality rates increased by 5.39 per 100,000 population during this time (60.72 to 66.11 per 100,000). Geographically weighted regression controlling for population demography and health indicators found higher median income and higher population density to be positively associated with majority (≥50%) HLTC population coverage and negatively associated with county-level nonoverdose mortality.

CONCLUSION

Over the past 15 years, the number of HLTC increased 31%, while population access to HLTC increased only 6.9%. High-level (I/II) trauma center designation is likely driven by factors other than population need. To optimize efficiency and decrease potential oversupply, the designation process should include population level metrics. Geographic information system methodology can be an effective tool to assess optimal placement.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level IV.
A systematic review and meta-analysis of sample size methodology for traumatic hemorrhage trials
Authors: Ghossein Jamie , Fernando Shannon M. , Rochwerg Bram , Inaba Kenji , Lampron Jacinthe , Tran Alexandre
Published: March 2023

BACKGROUND

Trauma hemorrhage remains the most common cause of preventable mortality in trauma. To guide clinical practice, RCTs provide high-quality evidence to inform clinical decision making. The clinical relevance and inferences made by RCTs are dependent on assumptions made during sample size calculation.

METHODS

To describe the quality of methodology for sample size determination, we conducted a systemic review RCTs evaluating interventions that aim to improve survival in adults with trauma-related hemorrhage. Estimated and actual outcome data are compared, including components of sample size determination.

RESULTS

A total of 13 RCTs were included. We noted a high rate of negative trial results (11 of 13 studies). Most studies were multi-center and conducted in North America, evaluating patients with blunt and penetrating injuries. The criteria for hemorrhagic shock varied across studies. All studies did not accurately estimate the mortality rate during sample size calculation. All but one study overestimated the mortality reduction during sample size calculation; the median absolute mortality reduction was 3%, compared with a target of 10%. Only the CRASH-2 study used a minimal clinically important different for treatment effect target. No RCTs employed prognostic enrichment. Most studies were terminated (8 of 13), mainly for futility.

CONCLUSION

Taken together, this review highlights that current clinical trial methodology is limited by imprecise control group risk estimates, overly optimistic treatment effect estimates, and lack of transparent justification for such targets. These limitations result in studies at high risk for futility and potentially premature abandonment of promising therapies. Given the high morbidity and mortality of trauma-related hemorrhage, we recommend that future conduct of trauma RCTs incorporate (1) prognostic enrichment to inform baseline risk, (2) justify target treatment differences based on clinical importance and realistic estimates of feasibility, and (3) be transparent and provide justification for the assumptions made.

LEVEL OF EVIDENCE

Systematic Review/Meta-Analysis; Level III.
Multivariate prediction of cognitive performance from the sleep electroencephalogram
Authors: Ujma Péter P. , Bódizs Róbert , Dresler Martin , Simor Péter , Purcell Shaun , Stone Katie L. , Yaffe Kristine , Redline Susan
Published: March 2023

Human cognitive performance is a key function whose biological foundations have been partially revealed by genetic and brain imaging studies. The sleep electroencephalogram (EEG) is tightly linked to structural and functional features of the central nervous system and serves as another promising biomarker. We used data from MrOS, a large cohort of older men and cross- validated regularized regression to link sleep EEG features to cognitive performance in cross- sectional analyses. In independent validation samples 2.5-10% of variance in cognitive performance can be accounted for by sleep EEG features, depending on the covariates used. Demographic characteristics accounted for more covariance between sleep EEG and cognition than health variables, and consequently reduced this association by a greater degree, but even with the strictest covariate sets a statistically significant association was present. Sigma power in NREM and beta power in REM sleep were associated with better cognitive performance, while theta power in REM sleep was associated with worse performance, with no substantial effect of coherence and other sleep EEG metrics. Our findings show that cognitive performance is associated with the sleep EEG (r=0.283), with the strongest effect ascribed to spindle- frequency activity. This association becomes weaker after adjusting for demographic (r=0.186) and health variables (r=0.155), but its resilience to covariate inclusion suggest that it also partially reflects trait-like differences in cognitive ability.
Predicting Imminent Health Outcomes from Common Lab Results
Authors: Cerejo Jorge , Neves Bernardo , da Silva Nuno André , Moreira José Maria , Silva Mário J.
Published: March 2023

In recent years, most hospitals have implemented Electronic Health Records to manage and integrate a wide range of medical information, including diagnostics, medication admission and laboratory test results. Certain laboratory variables may serve as indicators of a patient’s clinical deterioration, making laboratory data a valuable tool for identifying high-risk patients. This work introduces a framework for predicting imminent health outcomes (IHO) of multimorbidity patients using laboratory test data. Our cohort includes 322,316 multimorbidity patients that performed laboratory tests in a large teaching hospital between January 2007 and August 2021. Two Imminent Health Outcomes predictive tools were developed. The first considers all patients in the dataset. The second was developed using a subset of patients with Heart Failure (HF) as the main comorbidity (5% of the entire dataset), considering that HF is a highly prevalent syndrome in multimorbidity patients. This predictive model achieved a reasonable predictive performance (AUROC= 0.718, 95% CI 0.708-0.756, andAUPRC= 0.663, 95% CI 0.630-0.701). C-reactive protein and NT-proBNP are the lab tests that most positively contribute to the prediction of IHO. The IHO predictive tool has the potential to help the medical team identify patients at high-risk of an imminent adverse event, highlighting the laboratory variables that are most contributing to the deterioration of the patient.
Cardiac Rehabilitation Participation in Heart Failure Over Time: An Analysis of the Colorado All Payer Claims Database
Authors: Deng Lubin R. , Polsinelli Vincenzo B. , Kini Vinay , Wilson Morgan , Peterson Pamela , Bekelman David B. , Flint Kelsey M.
Published: March 2023

Background

Despite CMS coverage expansion supporting cardiac rehabilitation (CR) in patients with heart failure (HF) in 2014, data suggest that utilization among patients with HF is low. We describe CR participation and adherence among HF patients in Colorado.

Methods

Data from the Colorado All-Payer Claims Database from 2010-2018 were used. Patients with HF were identified by ≥2 claims with a HF diagnosis code, then grouped by type of HF (HFrEF, HFpEF, unspecified). CR participation and adherence were identified using CR CPT codes. Participation rates were calculated by quarter of each year. Cochran-Armitage tests determined whether temporal trends were significant. Association between CR participation and payer source was examined in adjusted logistic regression models.

Results

263,476 patients with HF were identified. 4.77% of all HF patients attended CR at least once; this result was similar for HFpEF (4.35%), unspecified HF (4.15%), and higher in the HFrEF group (8.25%). Overall adherence was poor (median 8 visits, IQR 3-18; full adherence=36 visits). CR participation over time increased (P<0.01) for all HF patients. Compared to patients with commercial insurance, patients with Medicare, Medicaid, or Medicare Advantage were less likely to have participated in CR at least once (P<0.01). Race, sex and presence of another indication for CR were also associated with at least one CR visit (P<0.01).

Conclusions

In the state of Colorado, CR participation improved from 2010-2018 among all patients with HF. Our data suggest that payer source, race, sex and presence of another indication for CR drive CR participation in patients with HF.
Leveraging genetic diversity to identify small molecules that reverse mouse skeletal muscle insulin resistance
Authors: Masson Stewart W.C. , Madsen Søren , Cooke Kristen C. , Potter Meg , Diaz-Vegas Alexis , Carroll Luke , Thillainadesan Senthil , Cutler Harry B. , Walder Ken , Cooney Gregory J. , Morahan Grant , Stöckli Jacqueline , James David E.
Published: March 2023

Systems genetics has begun to tackle the complexity of insulin resistance by capitalising on computational advances to study high-diversity populations. “Diversity Outbred in Australia (DOz)” is a population of genetically unique mice with profound metabolic heterogeneity. We leveraged this variance to explore skeletal muscle’s contribution to whole-body insulin action through metabolic phenotyping and skeletal muscle proteomics of 215 DOz mice. Linear modelling identified 553 proteins that associated with whole-body insulin sensitivity (Matsuda Index) including regulators of endocytosis and muscle proteostasis. To enrich for causality, we refined this network by focussing on negatively associated, genetically regulated proteins, resulting in a 76-protein fingerprint of insulin resistance. We sought to perturb this network and restore insulin action with small molecules by integrating the Broad Institute Connectivity Map platform andin vitroassays of insulin action using the Prestwick chemical library. These complimentary approaches identified the antibiotic thiostrepton as an insulin resistance reversal agent. Subsequent validation inex vivoinsulin resistant mouse muscle, and palmitate induced insulin resistant myotubes demonstrated potent insulin action restoration, potentially via up-regulation of glycolysis. This work demonstrates the value of a drug-centric framework to validate systems level analysis by identifying potential therapeutics for insulin resistance.
Decoding Duchenne muscular dystrophy transcriptome to single nuclei level reveals clinical-genetic correlations
Authors: Suárez-Calvet Xavier , Fernández-Simón Esther , Natera Daniel , Jou Cristina , Pinol-Jurado Patricia , Villalobos Elisa , Ortez Carlos , Monceau Alexandra , Schiava Marianela , Verdu-Díaz José , Clark James , Laidler Zoe , Mehra Priyanka , Gokul-Nath Rasya , Alonso-Perez Jorge , Marini-Bettolo Chiara , Tasca Giorgio , Straub Volker , Guglieri Michela , Nascimento Andrés , Diaz-Manera Jordi
Published: March 2023

The cellular and molecular consequences of lack of dystrophin in humans are only partially known, which is crucial for the development of new therapies aiming to slow or stop the progression Duchenne and Becker muscular dystrophies. We analyzed muscle biopsies of DMD patients and controls using single nuclei RNA sequencing (snRNAseq) and correlated the results with clinical data. DMD samples displayed an increase in regenerative fibers, satellite cells and fibro-adipogenic progenitor cells (FAPs) and a decrease in slow fibers and smooth muscle cells. Samples from patients with stable mild weakness were characterized by an increase in regenerative fibers, while those from patients with progressive weakness had fewer muscle fibers and increased FAPs. DMD muscle fibers displayed a strong regenerative signature, while DMD FAPs upregulated genes producing extracellular matrix and molecules involved in several signaling pathways. An analysis of intercellular communication profile identified FAPs as a key regulator of cell signaling in DMD samples. We show significant differences in the gene expression profiled of the different cell populations present in DMD muscle samples compared to controls.
KIF16B mediates anterograde transport and modulates lysosomal degradation of the HIV-1 envelope glycoprotein
Authors: Weaver Nicholas , Hammonds Jason , Ding Lingmei , Lerner Grigoriy , Dienger-Stambaugh Krista , Spearman Paul
Published: March 2023

The human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) is incorporated into virions at the site of particle assembly on the plasma membrane (PM). The route taken by Env to reach the site of assembly and particle incorporation remains incompletely understood. Following initial delivery to the PM through the secretory pathway, Env is rapidly endocytosed, suggesting that recycling is required for particle incorporation. Endosomes marked by the small GTPase Rab14 have been previously shown to play a role in Env trafficking. Here we examined the role of KIF16B, the molecular motor protein that directs outward movement of Rab14-dependent cargo, in Env trafficking. Env colocalized extensively with KIF16B+ endosomes at the cellular periphery, while expression of a motor-deficient mutant of KIF16B redistributed Env to a perinuclear location. The half-life of Env labeled at the cell surface was markedly reduced in the absence of KIF16B, while a normal half-life was restored through inhibition of lysosomal degradation. In the absence of KIF16B, Env expression on the surface of cells was reduced, leading to a reduction in Env incorporation into particles and a corresponding reduction in particle infectivity. HIV-1 replication in KIF16B knockout cells was substantially reduced as compared to wildtype cells. These results indicate that KIF16B regulates an outward sorting step involved in Env trafficking, thereby limiting lysosomal degradation and enhancing particle incorporation.

IMPORTANCE

The HIV-1 envelope glycoprotein is an essential component of HIV-1 particles. The cellular pathways that contribute to incorporation of envelope into particles are not fully understood. Here we identify KIF16B, a motor protein that directs movement from internal compartments toward the plasma membrane, as a host factor that prevents envelope degradation and enhances particle incorporation. This is the first host motor protein identified that contributes to HIV-1 envelope incorporation and replication.
Frequent emergence of resistance mutations following complex intra-host genomic dynamics in SARS-CoV-2 patients receiving Sotrovimab
Authors: Palomino-Cabrera Rosalía , Tejerina Francisco , Molero-Salinas Andrea , Ferris María , Veintimilla Cristina , Catalán Pilar , Rodríguez Macias Gabriela , Alonso Roberto , Muñoz Patricia , de Viedma Darío García , Pérez-Lago Laura
Published: March 2023

The emergence of the Omicron variant of SARS-CoV-2 represented a challenge to the treatment of COVID-19 with monoclonal antibodies. Only Sotrovimab maintained partial activity, allowing it to be used in high-risk patients infected with the Omicron variant. However, the reports of resistance mutations to Sotrovimab call for efforts to better understand the intra-patient emergence of this resistance. A retrospective genomic analysis was conducted on respiratory samples from immunocompromised patients infected with SARS-CoV-2 who received Sotrovimab at our hospital between December 2021 and August 2022. The study involved 95 sequential specimens from 22 patients (1-12 samples/patient; 3-107 days post-infusion (Ct ≤ 32)). Resistance mutations (in P337, E340, K356, and R346) were detected in 68% of cases; the shortest time to detection of a resistance mutation was 5 days after Sotrovimab infusion. The dynamics of resistance acquisition were highly complex, with up to 11 distinct amino acid changes in specimens from the same patient. In two patients, the mutation distribution was compartmentalized in respiratory samples from different sources. This is the first study to examine the acquisition of resistance to Sotrovimab in the BA.5 lineage, enabling us to determine the lack of genomic or clinical differences between Sotrovimab resistance in BA.5 relative to BA.1/2. Across all Omicron lineages, the acquisition of resistance delayed SARS-CoV-2 clearance (40.67 vs 19.5 days). Close, real-time genomic surveillance of patients receiving Sotrovimab should be mandatory to facilitate early therapeutic interventions.
Stitch with Which? Absorbable vs Nonabsorbable Suture for Skin Closure – A meta-analysis
Authors: Desai Dev
Published: March 2023

Background

It has been taught as a fundamental value that for skin sutures and wound closure, non-absorbable sutures should be used without many research papers supporting its higher efficacy with decreased would infection, decreased wound dehiscence and decreased skin scarring. The optimal suture material type still remains a myth.

Objective

This study aimed to compare the outcomes of absorbable versus non-absorbable sutures for skin closure

Methods

A Systemic-review was performed with randomized controlled trials (RCTs) and Cohort studies that compared outcomes of absorbable versus non-absorbable sutures for skin closure.

Results

A total of 5096 patients in 27 RCTs analyzed. There was no significant difference between absorbable sutures and non-absorbable sutures in the incidence of wound infections, scar formation and wound dehiscence. The results of both groups are quite comparable with nil heterogeneity.

Conclusions

Absorbable sutures for skin closure were not inferior to nonabsorbable sutures. It should be recommended due to its great cost and time savings. Well-designed RCTs with sufficient follow-ups are needed to adequately clarify whether better cosmetic results can be achieved using intradermal absorbable sutures.
Mobile Stroke Unit Treatment Times and Transport Frequency in a Suburban Setting
Authors: Vargas Alejandro , Zobel Rebecca , Cherian Laurel J. , Dafer Rima M. , Osteraas Nicholas D. , Song Sarah Y. , Cichon Mark E. , Conners James J.
Published: March 2023

Background

The majority of Mobile Stoke Units (MSUs) operate in European and United States urban cities. Questions remain on the cost-effectiveness, setting (urban, suburban, or rural), infrastructure and support, and reimbursement of these units. We present our experiences of a single-center MSU in a suburban setting, with treatment times, challenges, and possible future directions of alternative methods of care.

Methods

Retrospective analysis of prospectively collected data from Mobile Stroke Unit calls for service and Get With The Guidelines-Stroke data from two primary stroke centers from December 2017 through February 2020 comparing patients receiving intravenous thrombolysis and treatment times.

Results

There were no differences in age, sex, medical history, or stroke severity between MSU transport when compared to standard transport. There were differences in patient racial and ethnic demographics between groups, with higher white race and Hispanic ethnicity. Door-to-needle time was 48.9 minutes for patients seen on the Rush MSU versus 67.2 minutes for patients seen via traditional EMS transport (p=0.04).

Conclusions

The Rush MSU demonstrated significant reduction of acute ischemic stroke treatment time with intravenous thrombolysis, but did not demonstrate the patient volume necessary to justify continued operation. Suburban and rural regions do benefit from pre-hospital stroke evaluation, however the ideal method for a cost-effective strategy is still unknown.